Chapter 5: Membrane Dynamics

types of channel proteins

(1) gated channels (2) open channels

each kilogram of water has a volume of ___L

1

The resting membrane potential is due mostly to _____

Potassium

huh? ? Once you know the total body's osmolarity (concentration), you also know the ECF and ICF osmolarity because they are the same???

oh nvm, makes sense

open channels are AKA

water pores leak channels

cystic fibrosis symptoms

weight loss respiratory problems digestive ailments

types of gated channels

(1) chemically gated (2) Voltage gated (3) mechanically gated

Transepithelium movement of glucose involves three systems:

1) Na+-glucose secondary active transporter (SGLT) through apical membrane (from lumen) -- into epithelial cell 2) movement of Na+ and glucose into ECF (separate transporters) --- Na+ moves out through sodium potassium pump (primary) --- GLUT Transporters (glucose)

many primary active transporters are known as

ATPases they are enzymes!? because they hydrolyze ATP in the process

example of how change in surface area has impactful physiological effects: lung disease emphysema

As lung tissue breaks down and is destroyed, the surface area available for diffusion of oxygen decreases Consequently, less oxygen can move into the body. in severe cases, the oxygen that reaches the cells is not enough to sustain any muscular activity and the patient is confined to bed.

permeability: size and shape

As molecular size increases, membrane permeability decreases.

Na+ is concentrated more where? -- lumen of kidney/intestine -- kidney/intestine epithelial cell -- ECF

ECF lumen

where are GLUT transporters found

GLUT transporters are found on all cells of the body.

Na+-K+-2Cl- (NKCC) symporter

I think pumps all of them in, which is why its considered electrically neutral

list order of solute concentrations in ECF highest to lowest Cl Na HCO3 K and proteins

Interstitial: Na > Cl > HC03 > K (*no proteins*) plasma: Na > Cl > Proteins > HCO3 > K

the most important non-penetrating solute in physiology is

NaCl (functionally non penetrating because some still leak over)

Exocytosis involves two families of proteins:

Rabs SNAREs

bulk flow

The movement of a fluid due to a difference in pressure between two locations. gas is considered a liquid

net result of Na+-glucose secondary active transport

The net result is the entry of glucose into the cell against its concentration gradient, coupled to the movement of Na+ into the cell down its concentration gradient.

Material leaves cells by the process known as

exocytosis

SNAREs

faciliate membrane *fusion*

potassium ions are more concentrated

inside the cell

GLUT1 is found where

most cells of body

GLUT transporters

move glucose and related hexose sugars across membranes

coconut water IV analysis

not ideal solution useful for emergencies isosmotic to human plasma hypotonic with Na+ concentrations much lower than normal ECF and high concentrations of glucose and fructose along with amino acids

CFTR chloride channel

only ion channel in ABC super family defective or absent in cystic fibrosis

penetrating vs. non-penetrating solutes

pentrating: can pass membrane non-penetrating: can't pass membrane

The selectivity of a channel is determined by .....

the diameter of its central pore and by the electrical charge of the amino acids that line the channel

osmotic equilibrium is reached because of

the freely movement of water

paracellular

through tight junctions

(T/F) Open channels have gets, just spend most of their time with them open

true!!!

digitalis

strengthens the contraction of the heart muscle, slows the heart rate, and helps eliminate fluid from body tissues

apical

surface of the epithelial cell that faces the lumen of an organ

beta cells of pancreas do what .... by...

synthesize insulin and store it in cytoplasmic secretory vesicles to later release into blood when glucose levels are high by facilitated diffusion exocytosis opening and closing of ion channels by ligands and membrane potential

tonicity

term used to describe a solution and how that solution would affect cell volume if the cell were placed in the solution and allowed to come to equilibrium

Fick's law of Diffusion says what...

the diffusion rate increases when surface area, the concentration gradient, or the membrane permeability increase:

primary active transport (direct)

the energy to push molecules against their concentration gradient comes directly from the high-energy phosphate bond of ATP.

a source of potential energy in the sodium potassium pump is...

the high sodium concentration outside the cell and low concentration inside the cell

osmolarity

the number of osmotically active particles (*ions or intact molecules*) per liter of solution. i.e. osmoles /L or OsM

if the membrane potential difference is increasing, what does that mean

the value of Vm must be moving away from the ground value of 0 and becoming more negative

tonicity describes

the volume change of a cell

are competitive inhibitors bad ? can they be useful

they can be bad, but also useful An example involves gout, a disease caused by elevated levels of uric acid in the plasma. Normally kidney organic anion transporter (OAT) reclaims urate (the anion form of uric acid) from the urine and returns the acid to the plasma. However, if an organic acid called probenecid is administered to the patient, OAT binds to probenecid instead of to uric acid, preventing the reab- sorption of urate. As a result, more urate leaves the body in the urine, lowering the uric acid concentration in the plasma.

cystic fibrosis physiological symptoms (like in cells and stuff)

thick and dehydrated mucus

transcellular

through cells

why isn't disaccharide maltose moved across membrane

too big it inhibits glucose from binding GLUT transporters, but once bound its too big to transport

proteins and other large anions are concentrated inside plasma, but why can't they pass leaky exchange epithelium of blood vessels

too big, so they are absent in interstitial fluid which is why plasma and interstitial fluid are at disequilibrium

ex: Membrane enzymes on internal surface of cells play important rile in

transferring signals from the extracellular environment to the cytoplasm

(T/F) All secondary active transport ultimately depends on primary active transport because the concentration gradients that drive secondary transport are created using energy from ATP.

true

(T/F) Apical membrane of epithelial cells is often folded into microvilli to increase surface area

true

(T/F) Atoms are electrically neutral

true

(T/F) Carrier transporters can be both facilitated and active transport

true

(T/F) Carrier-Mediated Transport Exhibits Specificity, Competition, and Saturation

true

(T/F) Diseases can be caused through paracellular pathway

true

(T/F) Facilitated diffusion has the same properties as simple diffusion

true

(T/F) Membrane proteins get to membrane through exocytosis

true

(T/F) electrical gradient is created by active transport

true

(T/F) in facilitated diffusion, if the gradient reverses so does the direction of transport (same as diffusion)

true

(T/F) the vast majority of solutes cross membranes with the help of membrane proteins

true

carrier proteins transport only thousands of molecules while channels transport millions

true

(T/F) epithelia have the ability to change the "tightness" of their junctions

true :o

(T/F) pyruvate and lactate are organic molecules that carry charge and are considered ions

true :o

(T/F) Changes in ion permeability change membrane potential

true duh

(T/F) Antiport carriers are primary active transporters

true!

(T/F) Transcellular transport uses a combination of active and passive transport mechanisms

true; Protein-mediated transcellular transport is usually a two- step process, with one "uphill" step that requires energy and one "downhill" step in which the molecule moves passively down its gradient.

(T/F) ion channels may be specific for one ion or may allow ions of similar size and charge to pass

true; ex: there are Na + channels, K + channels, and nonspecific monovalent ("one-charge") cation channels that transport Na + , K + , and lithium ions (Li + ).

(T/F) Cholesterol always travels with a lipoprotein to make it soluble

true; LDL (low density lipoprotein)

(T/F) Exocytosis like endocytosis is constitutive

true; exocytosis is the opposite of endocytosis

(T/F) oxygen, CO2, and lipids move easily across most cell membranes

true; in addition to steroids and other lipophilic molecules

*NOTE* cell membranes of some sections of the *kidney* are essentially impermeable to water

unless water channel proteins are inserted

secondary active transport (indirect)

uses potential energy stored in the concentration gradient of one molecule to push other molecules against their concentration gradient.

describe movement of plasma protein across epithelial cell

uses: receptor mediated endocytosis (caveole), vesicular transport with help from *microtubules*, exocytosis 1) Plasma proteins are concentrated in caveolae, which then undergo *receptor mediated endocytosis* and form vesicles. 2) Vesicles cross the cell with help from the cytoskeleton *microtubules*. 3) Vesicle contents are released into interstitial fluid by exocytosis.

Transepithelial transport can use ion movement through channels in addition to carrier-mediated transport. Give an example: (HINT: involves K+ and Na+ and Cl-)

using *Na+-K+-2Cl- (NKCC) symporter* -- brings K+ from lumen into epithelial cell (K+ is more concentrated in the cell and less in lumen) -- need kinetic energy from Na+ concentration gradient (high in lumen, low in cell) to bring potassium in -- K+ can move out the epithelial cells into ECF through leaky K+ channels -- Na+ needs to be pumped out of cell using sodium potassium pumo

Transcytosis

vesicles to cross epithelium! combination of endocytosis and exocytosis

which disease processes are caveolae thought to be a part of

viral and parasitic infections muscular dystrophy (in protein caveolin)

beta cells of pancreas have what type of transporters to regulate insulin release

voltage gated Ca2+ channel K+ leak channel

lipophobic molecules include

water nutrients ions polar molecules

membrane recycling

when vesicles that come into the cytoplasm by endocytosis are returned to the cell membrane

can gap junctions and nuclear pore complexes be considered large forms of channels?

yes

is it possible to find carrier proteins of more than two molecules?

yes

can GLUT transporters reverse?

yes ex: blood glucose levels are high, liver cells bring glucose into their cells.

can body absorb Na+ and K+ at the same time from the lumen of the intestine or the kidney ?

yes, using *Na+-K+-2Cl- (NKCC) symporter* (described above, but doesnt incorporate how Cl is integrated)

In all, Diffusion is faster:

—along higher concentration gradients. —over shorter distances. —at higher temperatures. —for smaller molecules.

Factors affecting rate of diffusion through a cell membrane: (5)

• Lipid solubility • Molecular size • Concentration gradient • Membrane surface area • Composition of lipid layer

rules for predicting tonicity when knowing osmolarity only

(1) If the cell has a higher concentration of nonpenetrating solutes than the solution, there will be net movement of water into the cell. The cell swells, and the solution is hypotonic. (2) If the cell has a lower concentration of nonpenetrating solutes than the solution, there will be net movement of water out of the cell. The cell shrinks, and the solution is hypertonic. (3) If the concentrations of nonpenetrating solutes are the same in the cell and the solution, there will be no net movement of water at equilibrium. The solution is isotonic to the cell

membrane proteins have four major functions: structural proteins have three major roles, what are they?

(1) connect membrane to cytoskeleton to maintain cell shape. (ex: microvilli of transporting epithelial) (2) create cell junctions that hold tissues together (3) attach cells to the extracellular matrix by linking cytoskeleton fibers to extracellular collagen and other protein fibers

simple diffusion properties (in addition to the 7 just discussed)

(1) rate of diffusion depends on the ability of the diffusing molecule to dissolve in the lipid layer of the membrane (2) rate of diffusion across a membrane is directly proportional to the surface area of the membrane

What factors influence membrane permeability? an equation that describes this?

(1) size (and shape of large molecules) (2) lipid solubility (3) composition of bilayer

membrane proteins have four major functions

(1) structural (2) enzymes (3) receptors (4) transports

types of carrier proteins

(1) uniport carriers (2) symport carriers (3) antiport carriers

*RULES* for osmolarity and tonicity body analysis

*FIRST ONLY INCORPORATE NON PENETRATING INTO THE ICF AND ECF CALCULATION* the volume doesn't change when you are incorporating *penetrating* solutes because it will go to equilibrium. I think solutes still change, but just even out?

simple diffusion properties: rate of diffusion across a membrane is directly proportional to the surface area of the membrane.

*pay attention to this cause it isnt what you thought* larger the membrane's surface area, the more molecules can diffuse across per unit time.

glucose is concentrated more where? -- lumen of kidney/intestine -- kidney/intestine epithelial cell -- ECF

- epithelial cell

what causes changes in membrane potential

-- Na+, Ca2+, Cl-, and K+

describe transepithelium movement of glucose in more detail

-- glucose concentration is lower both at the lumen and ECF, which is why we need SGLT - Na+ transporter to move glucose against its concentration gradient into the epithelial cell (uses kinetic energy from Na+ gradient) -- Na+ concentration is higher in the lumen and also in the ECF. It's low inside the epithelial cell (ICF) -- once in the cell, the ECF has lower concentration of glucose, so it just moves down its gradient using GLUT (diffusion) -- Na+ concentration is lower in the cell than in the ECF, so needs ATP to get moved back into ECF. (primary with sodium potassium pump)

following a meal, what happens to beta cells of pancreas

-- glucose enters through GLUT channels -- metabolism increases (glycolysis & citric acid cycle) -- ATP production increases -- Katp channels close because ATP binds, K+ stop going out of the cell -- cell depolarizes because of positive K+ inside -- resting membrane potential difference changes, causing voltage gated ca2+ channels to open -- calcium ions enter the cell from ECF *down electrochemical gradient* -- Ca2+ bind to proteins that *commence exocytosis* of insulin containing endosomes -- insulin released into extracellular space

cation channel have what type of charged pore/amino acids?

-- negatively charge pore/amino acid

membrane recycling example using transporters

-- transporters can be destroyed in lysosomes -- or can be kept in endosomes ready to be reinserted back into membrane when there's a signal

nerve and muscle cells will record a resting membrane potential between ____ and ____, which indicates...

-40 and -90 mV that the ICF is negative relative to ECF

1 M of glucose to OsM is

1 OsM

two factors influence a cell membrane's potential:

1) *concentration* gradients of different ions across membrane 2) *permeability* of membrane to those ions

mechanism of Na+ - K+ pump

1) 3 Na+ bind on ICF to high affinity sites on protein 2) ATP attaches to preoteins 3) ATPase is phosphorylated with Pi from ATP 4) protein changes conformation 5) Na-binding sites lose their affinity for Na+ and release 3 Na+ into ECF. 6) High-affinity binding sites for K+ appear. 7) 2 K+ from ECF bind to high-affinity sites, Pi loses affinity and comes off protein 8) Protein changes conformation 9) K-binding sites lose their affinity for K+ and release 2 K+ into ICF. 10) High-affinity binding sites for Na+ appear.

receptor-mediated endocytosis steps

1) extracellular ligands that will be brought into the cell bind to their membrane receptors 2) receptor-ligand complex migrates along the cell surface until it encounters a coated pit 3) Once the receptor-ligand complex is in the coated pit, the membrane draws inward, or invaginates. 4) The vesicle pinches off from the cell membrane and becomes a cytoplasmic vesicle. Clathirin is released and travels back to membrane 5) in the vesicle, the receptor and ligand separate, leaving the ligand inside an endosome 6) The endosome moves to a lysosome if the ligand is to be destroyed *or* the Golgi complex if the ligand is to be processed 7) Meanwhile, the ligand's membrane-bound receptors may be reused in a process known as membrane recycling. 8) vesicle moves back to cell membrane and fuses through *exocytosis*

how do endocytosis and phagocytosis differ

1) in endocytosis the membrane surface indents rather than pushes out 2) vesicles formed from endocytosis are much smaller 3) some endocytosis is constitutive; that is, it is an essential function that is always taking place, whereas phagocytosis must be triggered by the presence of a substance to be ingested.

exocytosis regulated steps

1) increase in intracellular Ca2+ (*signal*) 2) interacts with calcium sensing protein m initiates secretory vesicle docking and fusion

How can cells increase their transport capacity and avoid saturation?

1) increase the number of carriers in the membrane. 2)

Remember the following important principles when you deal with electricity in physiological systems:

1) law of conservation of electrical charge 2) opposite attract, similar repel 3) energy needed to seperate (+ and -) 4) When separated positive and negative charges can move freely toward each other

size of a typical electrical signal passing down a neuron is

100 mV

how many membranes must transcellular pathway pass

2

how much energy does the sodium potassium pump use in terms of ATP

30% of what's produced

*NOTE* a *significant* change in membrane potential requires the movement of *very few ions* The concentration gradient does not have to reverse to change the membrane potential. For example, to change the membrane potential by 100 mV, only one of every 100,000 K+ must enter or leave the cell. *This is such a tiny fraction of the total number of K+ ions in the cell that the concentration gradient for K+ remains essentially unchanged.*

:!!!!!!!

*note* that when a positive ion moves across the membrane, negative ions will try to move with it because they are attracted, but cell membrane insulator will stop it

:(

*NOTE* Diffusion is *random* molecular motion *down* a concentration gradient chemical disequilibrium!!!!

:)

*NOTE* infants absorb maternal antibodies in breast milk using transcytosis. The antibodies are absorbed on the apical surface of the infant's intestinal epithelium and then released into the extracellular fluid

:)

*REMEMBER* cells can regulate number of protein carriers in membrane. if they want less of something, they just remove it

:)

most water movement across membranes takes place through protein channels, but that doesnt mean water doesnt slip by without them

:)

FROM NOW ON we will be talking about *beta cells of the pancreas*

:O

*NOTE* principles of diffusion apply to all biological membranes

:P

*remember* glucose is transported from lumen of kidney and intestine to ECF

:P

because biological solutions are dilute and little of their weight comes from solute, physiologists often use the terms osmolarity and osmolality interchangeably

:P

note beta cells of the pancreas use changes in the distribution of ions across cell membranes to trigger insulin secretion

:P

*REMEMBER* carrier proteins sometimes *CANNOT* transfer in both ways and only do so in one way

:o

how does tonicity relate osmolarity?

A hyposmotic solution is always hypotonic, no matter what its composition. An isosmotic solution may be isotonic or hypotonic, but can never be hypertonic Hyperosmotic solutions may be hypertonic, isotonic, or hypotonic.

simple diffusion properties: rate of diffusion depends on the ability of the diffusing molecule to dissolve in the lipid layer of the membrane (*permeability*)

AKA how permeable is the membrane to the molecule diffusing Most molecules in solution can mingle with the polar *phosphate-glycerol* heads of the bilayer but only nonpolar molecules that are lipid-soluble (lipophilic) can dissolve in the central lipid core of the membrane -- dumby this is why lipids can pass through the head of the phospholipid! It contains some nonpolar part like the glycerol!

*NOTE* There is overlap between the channel and carrier type transporters, both structurally and functionally. How? What's an example?

AQP; has been shown to act as both a water channel and a carrier for certain small organic molecule

K+ leaky channel in beta cells of pancreas closes when.... It's name is

ATP binds to it *ATP-gated K+ channel* or *Katp Channel*

most membrane transporters for organic solutes belong to one of two gene "superfamilies":

ATP-binding cassette (ABC) superfamily or the solute carrier (SLC) superfamily

permeability: lipid solubility

As lipid solubility of the diffusing molecule increases, membrane permeability to the molecule increases.

diffusion properties: diffusion is directly related to temperature

At higher temperatures, molecules move faster. generally doesnt affect humans because we have constant temperature

(T/F) All carrier proteins are used for facilitated diffusion

BIG FALSE! some are used in active transport

(T/F) Active transport move substances until equilibrium is reached

BIG FALSE!!! active transport creates a state of disequilibrium by making concentration differences more pronounced.

basolateral membrane

Below the tight junctions the cell surfaces that *face the extracellular fluid*

mechanism of Na+-glucose secondary active transporter (SGLT)

Both Na+ and glucose bind to the SGLT protein on the extra- cellular fluid side. 1) Sodium binds first and causes a conformational change in the protein that creates a high-affinity binding site for glucose 1 . 2) When glucose binds to SGLT 2 , the protein changes conformation again and opens its channel to the intracellular fluid side 3 . 3) Sodium is released to the ICF as it moves down its concentration gradient. 4) The loss of Na+ from the protein changes the binding site for glucose back to a low- affinity site, so glucose is released and follows Na+ into the cytoplasm 4 .

Why do cells need both channels and carriers?

Channel proteins allow more rapid transport across the membrane but generally are limited to moving small ions and water. carrier, while slower, can move larger molecules than channels can.

what happens to glucose when blood glucose levels are high

GLUT transporters on liver cells bring glucose into those cells

ouabain

Inhibits sodium pump (Na+/K+) by binding the K+ site. -- compound related to heart drug digitalis

major cation within cells is major cation outside cells is... major anion within cell are.. major anion outside cell are...

K+ Na+ phosphate ions and negatively charged proteins Cl-

secondary active transporters

Membrane transporters that use potential energy stored in concentration gradients to move molecules *uses the kinetic energy of one molecule moving down its concentration gradient to push other molecules against their concentration gradient*

Exocytosis

Process by which a cell releases large amounts of material

exocytosis

Releases Molecules (*lipophobic*) Too Large for Transport Proteins

repolarization

Return of the cell to resting state, caused by reentry of potassium into the cell while sodium exits the cell.

diffusion properties: Diffusion rate is inversely related to molecular weight and size

Smaller molecules require less energy to move over a distance and therefore diffuse faster *diffusion is inversely proportional to the radius of the molecule*: the larger the molecule, the slower its diffusion through a given medium.

The removal of Na+ from the cell is essential if glucose is to continue to be absorbed from the lumen. why?

The potential energy to run the SGLT symporter comes from the sodium concentration gradient, which depends on low intracellular concentrations of Na+

If GLUT transporters are everywhere, then why does the body need the SGLT Na+-glucose symporter?

The simple an- swer is that both SGLT and GLUT are needed to move glucose from one side of an epithelium to the other.

absorption give example

Transport of material from the lumen of an organ to the extracellular fluid ex: intestinal epithelium absorbs digested nutrients

if the membrane potential difference is decreasing, what does that mean

Vm is moving closer to the ground value of 0 mV and is becoming less negative.

can water pass through membrane by simple diffusion?

Water, although a polar molecule, may diffuse slowly across *some* phospholipid membranes experiments have shown that the small size of the water molecule allows it to slip between the lipid tails in some membranes *How readily water passes through the membrane depends on the composition of the phospholipid bilayer.*

*NOTE* Cells in which facilitated diffusion takes place can avoid reaching equilibrium by keeping the concentration of substrate in the cell low. what does this mean?

With glucose, for example, this is accomplished by phosphorylation As soon as a glucose molecule enters the cell on the GLUT carrier, it is phosphorylated to glucose 6-phosphate, the first step of glycolysis Addition of the phosphate group prevents build-up of glucose inside the cell and also prevents glucose from leaving the cell.

Does exocytosis require energy?

Yes, active transport ATP

depolarized

a condition in which the inside of a cell membrane is more positively charged than the outside membrane potential difference decreases

relative vs absolute scale for measuring electric potential

absolute: knowing ions on both sides of membrane relative: using a device to measure difference in electrical charge of one side of membrane set to 0, and measure the second side relative to first (scale is shifted left).

Phagocytosis

actin-mediated process by which a cell engulfs a bacterium or other particle into a large membrane-bound vesicle called a phagosome

electrical signals are known as

action potentials

epithelial cells are connected one another through

adhesive and tight junctions

active transport moves substances

against their concentration gradients

*NOTE* Gated channels spend most of their time in a closed state

allows channels to regulate the movement of ions through them

*NOTE* Sweat—a mixture of ions and water—is secreted into sweat ducts by the epithelial cells of sweat glands. As sweat moves toward the skin's surface through the sweat ducts, CFTR and Na+ channels move Cl- and Na+ out of the sweat and back into the body. This portion of the sweat gland epithelium *is not permeable to water*, and so normal reabsorption of NaCl creates sweat with a low salt content. Based on the information given, is CFTR protein on the apical or basolateral surface of the sweat gland epithelium?

apical The epithelial surface that faces the lumen of the sweat gland, which contains sweat, is the apical membrane. Therefore, the CFTR proteins are on the apical surface.

would the Na+-glucose symporter SGLT be found on apical or basolateral side? why?

apical polarized distribution of transporters allows the one-way movement of certain molecules across the epithelium.

water channels are made from what protein

aquaporin

would the Na+-K+-ATPase be found on apical or basolateral side? why?

basolateral membrane polarized distribution of transporters allows the one-way movement of certain molecules across the epithelium.

why is a cell's resting membrane potential closer to the EK of -90 mV than to the ENa of +60 mV

because 40 times more permeable to K+ than Na+

How does a beta cell 'know' that glucose levels have gone up and that it needs to release insulin?

beta cell's metabolism linked to electrical activity

carrier proteins

bind to the substrates that they carry but never form a direct connection between the intracellular fluid and extracellular fluid

carrier proteins transport by

binding specific substrates (glucose or amino acids -- large things) and changing conformation

in humans Phagocytosis happens in what cells

blood cells called phagocytes which specialize in eating bacteria and other foreign particles

what happens to glucose when fasting

blood glucose levels fall, liver cells convert their glycogen stores to glucose

cotrasnporter

carrier proteins that move more than one molecule

saturation

carriers are working at their maximum rate, and a *further increase in substrate concentration has no effect.*

antiport carriers

carry more than one type of molecule in different directions AKA exchangers

symport carriers

carry more than one type of molecule in same direction

membrane proteins have four major functions: Membrane enzymes

catalyze chemical reactions that take place either on the cell's external surface or just inside the cell.

we use goldman equation when

cell membrane is permeable to more than one ion

we use nernst equation when

cell membrane is permeable to only one ion

equilibrium potential (Eion)

cell that is permeable to only one ion, the membrane potential that exactly opposes the concentration gradient of the ion ex: the concentration gradient moving Na+ into the cell (150 mM outside, 15 mM inside) is exactly opposed by a positive membrane potential of +60 mV.

*NOTE* although the concentrations on both side of membrane are equal, they contain different number of solutes. Therfore, the body is in a _________ disequilibrium

chemical

permeability: composition of bilayer

cholesterol packing in membrane makes it *less permeable*

interstitial fluid lies between ...... it consists of ____% of the ECF

circulatory system and cells 75

the most common coated pits are

clathrin

endocytosis happens through

clathrin caveolae

voltage - gated ca2+ channel (in beta cells of pancreas) is (open/closed) at cell's resting membrane potential

closed

channel proteins structure

cluster of cylinders that create a pore through center

Receptor-mediated endocytosis takes place where

coated pits

osmolarity is a _____ property of solution, meaning

colligative it depends strictly on the number of particles per liter of solution

competitive inhibitors

competing molecule is not transported but merely blocks the transport of another substrate. ex: galactose on GLUT transporters

Caveolae functions

concentrate and internalize small molecules help in the transfer of macromolecules across the capillary endothelium participate in cell signaling

osmolality

concentration expressed as osmoles of solute per kilogram of water (not liters)

flux depends on

concentration gradient and membranes permeability to molecule

exocytosis: goblet cells

continuously release mucus by exocytosis

channel proteins

create water-filled passageways that directly link the intracellular and extracellular compartments

muscular dystrophy

degeneration of muscle and weakness

Entry of Ca2+ or Na+ (depolarizes/hyper-polarizes/repolarizes) the cell

depolarize -- makes membrane potential more positive

if the cell becomes less permeable to K+, exit of it (depolarizes/hyper-polarizes/repolarizes) the cell

depolarizes

flux

diffusion rate per unit surface area of membrane

insulin does what

directs other cells of the body to take up and use glucose, bringing blood concentrations down to pre-meal levels.

example of competitive inhibitors in GLUT transporters

disaccharide maltose galactose

diffusion properties: is a passive process

doesn't require input of energy from *outside* source uses *kinetic energy* possessed by molecules

Ion movement is influenced by ______ while molecules that are small and lipid soluble are influenced by ____

electrical gradient chemical gradient

The input of energy to transport ions across the membrane has created an

electrical gradient (difference in the net charge between two regions)

resting membrane potential difference (membrane potential) break it up into parts and tell what it means

electrical gradient between the intra and extracellular fluid 1) resting: electrical gradient is seen in all cells, even in those resting 2) potential: when atoms move down their electrical gradient, they release energy to do work. 3) difference: difference in amount of electrical charge inside and outside cell

electrical + chemical gradient =

electrochemical gradient

Defects in receptor mediated endocytosis can cause

elevated cholesterol in plasma cardiovascular disease because wont remove cholesterol from blood

gout disease

elevated levels of uric acid in the plasma

where are SGLT Na+-glucose symporter found?

epithelial cells of intestine or kidney to bring glucose in from *external environment*

*NOTE* small changes in membrane potential act as signals in *nonexcitable tissues*, such as endocrine cells

ex: beta cells of pancreas

hypercholesterolemia what is it? causes? predisposed to what?

excessive cholesterol in the blood not diet, but the failure of cells to take up cholesterol more specifically, LDL receptors dont take up LDL-cholesterol complex from the blood. predisposed to atherosclerosis

sodium chloride and bicarbonate are more concentrated on the (inta/extra)cellular side

extra

calcium is more concentrated in the...... even though....

extracellular fluid ER and mitochondria are highly concentrated with it too

in all.... Na, Cl, Ca, HCO3, are found in *high* amounts in _____ K is found in *high* amounts in ..... whereas proteins can be found in both places, bust mostly where in ECF?

extracellularly intracellularly plasma, because can't pass leaky epithelium to get to interstitial

SLC superfamily include

facilitated diffusion carriers secondary active transporters

(T/F) All ion transport proteins create an electrical gradient

false; Na+-K+-2Cl- (NKCC) symporter, is electrically neutral some make an even exchange, for each charge that enters cell, the same charge leaves

(T/F) Phagocytosis doesn't require energy from ATP

false; it does for the movement of the cytoskeleton and for the intracellular transport of the vesicles

(T/F) Passive transport does not use energy

false; it doesnt use ATP energy, but it does use molecular energy (kinetic energy/concentration gradient)

(T/F) To change membrane potential, have to change concentration gradients inside and outside cell drastically

false; only movement of a few ions can change the potential

(T/F) just nerve cells and muscle cells use electrical signals

false; other cells also use electrical signals for communcaition

(T/F) The carrier protein automatically opens to the other side when a molecule binds

false; there's a period where the carrier protein is closed to both sides before opening up

(T/F) transporting epithelial cells aren't polarized

false; they are because their apical and basolateral membranes have very different properties

(T/F) Ions such as Na+ and K+ can move just through channel proteins

false; they can move through carrier proteins too

(T/F) Faciliated diffusion uses carrier protein but not channel proteins

false; uses both

(T/F) when there's electrochemical disequilibrium, there's also osmotic disequilibrium

false; water can still move freely

simple diffusion follows which law

fick's law of diffusion

in all, _______ channels have more regulation

gated

what happens when the glucose concentration inside the liver cells builds up and exceeds the glucose concentration in the plasma

glucose leaves the cells on the reversible GLUT transporters.

in living systems, ECF is designated as _____ and assigned a charge of ____

ground; 0 mV

Atherosclerosis

hardening of the arteries due to cholesterol cholesterol in blood vessels blocks blood flow and contributes to heart attacks

Daniel is diagnosed with cystic fibrosis. Daniel must begin a regimen of pancreatic enzymes to be taken whenever he eats, for the rest of his life. In cystic fibrosis, thick mucus in the pancreatic ducts blocks the secretion of digestive enzymes into the intestine. Without artificial enzymes, he would starve. Why will Daniel starve if he does not take artificial pancreatic enzymes?

he won't get hungry because he isnt digesting Without digestive enzymes, Daniel cannot digest the food he eats. His weight loss over the past six months suggests that this has already become a problem. Taking artificial enzymes will enable him to digest his food.

Endocytosis can be highly selective or not at all, give examples

highly: receptor-mediated endocytosis not highly: pinocytosis, allowing liquid in

If solution A has a higher osmolarity (contains more particles per unit volume, is more concentrated) than solution B, we say that solution A is _____ to solution B. Solution B is _____ to solution A.

hyperosmotic hyposmotic

if the cell becomes more permeable to K+, exit of it (depolarizes/hyper-polarizes/repolarizes) the cell

hyperpolarizes

Entry of Cl- (depolarizes/hyper-polarizes/repolarizes) the cell

hyperpolarizes -- makes more negative

If the problem is dehydrated cells, the appropriate IV solution is ....

hypotonic

HCO3-/Cl- antiporter

in red blood cells electrically neutral exchange for each charge that enters cell, the same charge leaves

Ca+, Na+, and Cl- will move (in/out) if the cell becomes more permeable to them (down/up) their electrochemical gradient

in; down

coated pits

indentations where the cytoplasmic side of the membrane has high concentrations of protein

when separated charges cannot move through a material that separates them, it is called what

insualtor

the phospholipid bilayer is considered a (conductor/insulator)

insulator; keeps charges separated

GLUT4 is found where

insulin-regulated transporter of skeletal muscle

GLUT5 is found where

intestinal fructose transporter

What controls the opening and closing of chemically gated channels?

intracellular messenger molecules or extracellular ligands that bind to the channel protein

Fick's Law of Diffusion involves what?

involves surface area how readily molecule can dissolve in membrane (permeability) and concentration

what are examples of things that cant pass membrane easily

ions, most polar molecules, and very large molecules (such as proteins)

If the cell in the solution does not change size at equilibrium, the solution is

isotonic

how does cholesterol affect the membrane?>

it affects its permeability and allows it to cope with temperature changes

what does it mean for endocytosis to be constitutive?

it is an essential function that is always taking place

why is the Na+-K+-ATPase / Sodium potassium pump so important in animals?

it main- tains the concentration gradients of Na+ and K+ across the cell membrane

whats sodium potassium pump purpose

it maintains the concentration gradients of Na+ and K+ across the cell membrane

claudins

junctional proteins that can form large holes or pores that allow water, ions, and a few small uncharged solutes to move by the paracellular pathway

carriers composition

large, complex proteins with multiple subunits

In the resting cell, when glucose concentrations are low, the cell makes (more/less) ATP

less

how readily can water pass through the following membranes: - Membranes with high cholesterol content - Membranes with low cholesterol content why?

less permeable to water more permeable cholesterol has more surface area and blocks water from passing whereas the phospholipid tails have spaces between them

Adult women have _____ water per kilogram of body mass than men because they have more....

less; adipose tissue

receptors in Caveolae are anchored how

lipid anchored proteins

GLUT2 is found where

liver, kidney, and intestinal epithelial

secretion give example

material moves from the ECF to the lumen ex: salivary glands secrete saliva to help moisten the food you eat

conductor

material through which positive and negative charges move freely toward each other

membrane proteins have four major functions: transporters

membrane spanning proteins transport molecules across the membrane channel or carrier proteins

membrane transporters are

membrane-spanning proteins that help move *lipophobic* molecules across membranes.

gated channels have gate where?

middle of protein pore or cytoplasmic side of membrane protein

why are gases compressible

molecules are so far apart in space think about a balloon

diffusion properties: move from high to low concentration

molecules travel *down gradient* from high to low rate of diffusion depends on the magnitude of gradient (directly proportional)

in osmosis water moves to dilute the _____ concentrated solution. when does net movement of water stop

more one concentrations are equal

specificity in GLUT transporters what will it bind what will it not

move 6-carbon sugar *monosaccharides* (hexoses), such as glucose, mannose, galactose, and fructose will not trans- port the disaccharide maltose or any form of glucose that is not found in nature

uniport carriers

move only one kind of molecule

what happens if sodium potassium pump gets poisoned with ouabin

movement of glucose cross epithelium stops because sodium concentration will increase in ICF until equal to lumen and ECF, no kinetic energy to move glucose up its concentration gradient on the apical membrane

mediated transport

movement of molecules across membrane by binding to proteins

Diffusion

movement of molecules from an area of higher concentration of the molecules to an area of lower concentration of the molecules.*

Apical membrane AKA

mucosal membrane

electrogenic pump

name given to sodium potassium pump (Na+-K+-ATPase) because it helps maintain the electrical gradient in membrane by pumping out 3 Na+ and 2K+ in

ICF is (negative/positive) charge ECF is (negative/positive) charge

negative (anions dont have matching cations) positive (cations dont have matching anions)

law of conservation of electrical charge

net amount of electrical charge in any process is zero

GLUT3 is found where

neurons

what is sodium used for in the body

never cells use the gradient to transmit electrical signals epithelial cells use it to drive uptake of nutrients, ions and water

if there is little ATP being made in pancreas beta cells (because low glucose levels) what does this mean for the channels?

no glucose being transported into beta GLUT channels (metabolism is low --> ATP low) the K+ leaky channels are open because there is no ATP binding to it, allowing K+ to leak out of it Voltage gated Ca2+ channels are closed no insulin secretion (inside beta pancreas cells inside endosomes)

What controls the opening and closing of voltage gated channels?

open and close when electrical state of cell changes

diffusion properties: Diffusion can take place in an open system or across a partition that separates two compartments

open: cologne bottle barrier: ICF and ECF

how can gout uric acid levels be dropped

organic acid called probenecid is administered to the patient, OAT binds to probenecid instead of to uric acid, preventing the reabsorption of urate. As a result, more urate leaves the body in the urine, lowering the uric acid concentration in the plasma.

membrane proteins have four major functions: receptors

part of signaling system binding of a receptor with its ligand usually triggers another event at the membrane

osmolarity describes the number of ______ while molarity describes ____

particles moles *note that bad thing about osmolarity is that it doesnt tell about composition of particles

energy requirements fall into no energy which is ______ transport yes energy which is _____ transport

passive active

facilitated diffusion

passive moves molecules down concentration gradient stops when concentrations are equal

Cells use two basic processes to import large molecules and particles:

phagocytosis and endocytosis

two ways to categorize how molecules move across membranes are defined by _____ and ____ requirements

physical and energy

phagosome

pinches off from the cell membrane and moves to the interior of the cell, where it fuses with a lysosome, and its enzymes destroy bacteria

liquid entering through endocytosis is called

pinocytosis

extracellular fluid is separated into

plasma interstitial fluid

if the channel amino acids are positively charged, what can pass? what can't?

positive ions are repelled and negative ions can pass through the channel

osmotic pressure

pressure that must be applied to prevent osmotic movement across a selectively permeable membrane

active transport can be divided into

primary (direct) secondary (indirect)

sodium potassium pump is what kind of transport process

primary active

Endocytosis

process by which a cell takes material into the cell by infolding of the cell membrane uses ATP

Receptor-mediated endocytosis transports what into the cell

protein hormones growth factors antibodies plasma proteins (serve as carriers for iron and cholesterol)

Rabs

protein which help vesicles *dock* to membrane

what does exocytosis transport

proteins too large to travel through channel/carrier proteins wastes left in lysosomes

ATPases are sometimes called

pumps ex: sodium-potassium pump (or Na+-K+-ATPase) -- same thing

kidney organic anion transporter (OAT)

reclaims urate (the anion form of uric acid) from the urine and returns the acid to the plasma.

exocytosis: fibroblasts in connective tissue

release collagen

endocrine cells

release their secretions (hormones) directly into body fluids

active transport

requires ATP or other outside source against concentration gradient

What controls the opening and closing of mechanically gated channels

respond to physical forces, such as *increased temperature or pressure* that puts *tension* on the membrane and pops the channel gate open.

ex: Membrane enzymes on external surface of cells lining *small intestine*

responsible for digesting peptides and carbohydrates

hyperpolarized

resting potential becomes more negative, the potential difference has increased membrane potential difference decreases

an important feature in the metabolism and homeostasis of glucose is

restriction of different GLUT transporters to different tissues

channel proteins are like doorways, whereas carrier proteins are like

revolving doors

SGLT-Na+-glucose transporter is what type of transport process

secondary active

what kind of work will an atom travelling down electrical gradient produce

sending electrical signals opening voltage gated channels

basolateral membrane AKA

serosal membrane

Caveolae

small flask-shaped indentations, another way endocytosis happens membrane regions with lipid rafts, membrane receptors, coat of membrane proteins called caveolins

In many cells, caveolae appear as

small indented pockets on the cell membrane

endocytosis creates (larger/smaller) vesicles than phago

smaller

The most common secondary active transport systems are driven by

sodium concentration gradient

by convention we always describe tonicity of _____ relative to ____

solution cell

do ligands always remain on cell surface?

sometimes other times they go in with the receptor-ligand either way an intracellular response occurs

to predict the movement of water into and out of cells, you must know the ______ of the solution. why?

tonicity because cell membranes are selectively permeable. meaning some solutes can actually pass

concentration

amount of solute per volume

how are very large lipophobic molecules moved into the cell?

- vesicles

how come an isosmotic solution can't be hypertonic ? tell what happens if there are no nonpenentrating solutes in the solution and if there are some

-- it can never have a higher concentration of nonpenetrating solutes than the cell. -- if there are no nonpenetrating solutes in the solution, the solution will be isotonic - if there are some nonpenetrating solutes in the solution it will be hypotonic

diffusion properties

1) passive process 2) molecules more from high to low concentration 3) Net movement occurs until equilibrium is reached 4) fast over short distances, slow over long 5) directly related to temperature 6) rate is inversely related to molecular weight and size 7) Diffusion can take place in an open system or across a partition that separates two compartments.

1 M (moles/L) of NaCl to OsM is

1.8 osmol NaCl/L because at body temperature some fail to separate. so instead of 2, we have a dissociation factor of 1.8

intracellular fluid is _____ of the total body of water... so extracellular is

2/3 1/3

for 70kg : ____L of ICF ____L of ECF (____L of plasma and ____L of interstitial fluid) what is this person total volume water?

28 14 3.5 10.5 60% is water (42L)

normal osmolarity of human body is

300 mOsM

*NOTE* THAT THIS DOESNT MEAN K+ ISNT FOUND IN ECF AND THAT Cl Na and HCO3 ARE NOT FOUND IN ICF they are, just in lower concentrations

:)

*REMEMBER* to determine tonicity, compare volumes of the original and the ICF or ECF

:)

We have a 3-liter body that is 300 mOsM. The ECF is 1 liter and the ICF is 2 liters. find out how much solute is in each of the two compartments

C = S/V

if Solution A = 1 OsM Glucose Solution B = 2 OsM Glucose Solution C = 1 OsM NaCl compare each one to each other in terms of isosmotic, hyposmotic, and hyperosmotic

Solution A: is hyposmotic to B is isosmotic to C Solution B: is hyperosmotic to A is hyperosmotic to B Solution C: is isosmotic to A is hyposmotic to B

Add an IV solution of 1 liter of 300 mOsM NaCl to this body. This solution adds 1 liter of volume and 300 mosmoles of NaCl.

The added solution was isosmotic (300 mOsM), and its nonpenetrating concentration was the same as that of the body's (300 mOsM NP). You would predict that the solution was isotonic. *That is confirmed with these calculations, which show no water entering or leaving the cells (no change in ICF volume).*

diffusion properties: rapid over short distances and slow over long

time required for a molecule to diffuse from point A to point B is proportional to the square of the distance from A to B

Why can't osmolarity be used to predict tonicity?

The reason is that the tonicity of a solution depends not only on its concentration (osmolarity) but also on the nature of the solutes in the solution. by nature = can they pass membrane?

If the situation requires fluid that remains in the extracellular fluid to replace blood loss, ..... IV is used

an isotonic IV solution is used

why is giving someone a glucose solution the same as giving them a slow infusion of pure water

because glucose 6-phosphate is the first step in the aerobic metabolism of glucose [p. 113]. The end products of aerobic glucose metabolism are CO2 and water.

why dont we use molarity to measure concentration?

because it doesn't take into account molecules that dissociate into particles molecules isn't the same as particles. so we use osmolarity

plasma is found in ... it consists of ____% of the ECF

circulatory system (liquid matrix of blood) 25

(T/F) Before we can predict whether osmosis will take place between any two solutions divided by a membrane, we must know the properties of the membrane and of the solutes on each side of it. We know this by measuring osmolarity

false; everything is true except "We know this by measuring osmolarity" we dont know particle composition through osmolarity

osmotic equilibirum

fluid concentrations are equal on the two sides of the membrane

blood flow as bulk flow

heart creates high pressure when it pump blood and pushes it away to regions of low pressure

physical requirements of molecules can be separated into *ionic/polar* which is transported by... *large* which is transported by... *small & lipid soluble* which is transported by...

help of proteins vesicles directly through phospholipid bilayer

in bulk flow, fluids flow from

high pressure to low pressure ex: blood flow (carries all substances dissolved and suspended in it)

Add 2 liters of a 500 mOsM solution. The solution is equal parts NaCl (nonpenetrating) and urea (penetrating), so it has 250 mosmol/L NaCl and 250 mosmol/L urea. Before working this problem, answer the following questions: (a) This solution is __________ osmotic to the 300 mOsM body. (b) What is the concentration of nonpenetrating solutes [NP] in the solution? _______________ (c) What is the [NP] in the body? ________ (d) Using the rules for tonicity in Table 5.4, will there be water movement into or out of the cells? If so, in what direction? (e) Based on your answer in (d), this solution is ________ tonic to this body's cells.

hyperosmotic 250 mOsm 300mOsm into cell hypotonic

If the cell loses water and shrinks at equilibrium, the solution is said to be

hypertonic.

If a cell placed in the solution gains water at equilibrium and swells, we say that the solution is ____ to cell

hypotonic

What does the slow rate of diffusion over long distances mean for biological systems?

in humans, nutrients take five seconds to diffuse from the blood to a cell that is 100 μm from the nearest capillary. At that rate, it would take years for nutrients to diffuse from the small intestine to cells in the big toe, and the cells would starve to death.

seniors, infants, adults put them in order of who has more water from greatest to least

infants > adults > seniors

the body is a whole is electrically neutral, but negative ions are found in ______, while positive in ______, resulting in a state of

intracellular extracellular electrical disequilibrium

what would happen if the solute was glucose?

is an unusual solute. Like all solutes, it first goes into the ECF. Over time, however, 100% of added glucose will enter the cells. When glucose enters the cells, it is phosphorylated to glucose 6-phosphate (G-6-P) and cannot leave the cell again. So although glucose enters cells, it is not freely penetrating because it stays in the cell and adds to the cell's nonpenetrating solutes.

Water is the most important molecule in the human body be- cause...

it is the solvent for all living matter.

Suppose you know the composition and osmolarity of a solution. How can you figure out the tonicity of the solution without actually putting a cell in it?

knowing the relative concentrations of nonpenetrating solutes in the cell and in the solution. Water will always move until the concentrations of nonpenetrating solutes in the cell and the solution are equal.

substances moving from plasma to interstitial fluid must pass

leaky exchange epithelium of capillary wall

Two properties of a molecule influence its movement across cell membranes:

lipid solubility size

osmosis

movement of water in response to a solute concentration gradient

Are liquids compressible? what about gases?

no; yes for water think about ice lol

tonicity depends on the concentration of (penetrating/nonpenetrating) solutes ONLY

nonpenetrating

how to overcome limitations of diffusion over distance?

organisms use various transport mechanisms that speed up the movement of molecules like the circulatory system

The intracellular and extracellular compartments of the body are in _______ equilibrium, but in ______ and _____ disequilibrium. all of which are considered dynamic ..... (meaning things are still moving)

osmotic chemical and electrical steady state

how can we make quantitative measurements of osmosis?

osmotic pressure (1) Place a piston into compartment B, which has a higher solute concentration than compartment A. By pushing down on the piston, you can keep water from flowing from A to B. (2) know the concentrations of the solutions with which we are dealing (osmolarity NOT molarity)

diffusion properties: Net movement of molecules occurs until the concentration is equal everywhere

reach dynamic equilibrium where concentration has equalized throughout the system but molecules continue to move

When cells die and cannot use energy, they obey

the second law of thermodynamics and return to a state of randomness that is marked by a loss of chemical equilibrium

isosmotic

two solutions contain the same number of solute particles per unit volume

is air flow in the lungs bulk flow

yes