Chapter 06 - Interactions between Cells and the Extracellular Environment

What is the general flow of information during cell signaling?

1) receptor-ligand binding 2) signal transduction (via secondary messengers) 3) cellular responses 4) changes in gene expression

GTP

A G-protein alpha subunit that has bound ____ is active and can catalyze the activation of other enzymes.

a) can be open at all times.

A channel protein a) can be open at all times. b) can move ions against their electro-chemical gradient. c) moves ions at a rate similar to that of a transporter. d) moves both anions and cations through the same channel.

1) Extracellular Factor (ECF) 2) Receptor 3) Intracellular Mediators 4) Nucleus

What are the cell signally components?

-- regulatory molecules released from neurons, endocrine glands, pancreatic beta-cells, wbc, adipocytes, osteocytes, endothelial cells lining blood vessels (all kinds of cell types)

What chemical signals are used to communicate between cells?

???

What is the physiological significance of the more than 30,000 different types of receptors for the different cells of the human body?

???

What molecular mechanism may mediate the diversity of the more than 30,000 different types of receptors for the different cells of the human body?

Because we would end up producing physiological responses that are not needed and this could cause disease

Why would we not want every ligand to bind to every receptor?

True

Will diffusion occur without a physical separation or across a permeable membrane?

Cell Signaling: Transcriptional Activation

-- 2.5 million end products from 1 receptor -- if more, number increased

Regulation of Blood Osmolality

-- constant osmolality must be maintained or neurons will be damaged...and the brain controls everything

Hypo-osmotic

-- one solution has a lower solute concentration and therefore a lower osmotic pressure than the other solution

Hypertonic

-- osmotically active solutes at a higher concentration than the other solution (water out of rbc causing it to shrink)

Intervenous Infusion

-- NaCl --> 0.15 Osm unit + 0.15 Osm unit = 0.3m (same as 0.3m glucose solution) -- both 0.3 Osm glucose and 0.15 saline (have same osmolality and osmotic pressure so blood cells will be unaffected) -- ex. if a membrane separates a 0.3m glucose solution and a 0.15m NaCl solution, there will be no net movement of water = isotonic (because equal # of solute particles on either side) -- **remember molality (m) directly correlates with Osm units (1m = 1 Osm)

Diffusion of Gases: Simply No Barrier

-- O2 from extracellular environment into tissue cells -- CO2 from tissue cells into extracellular environment -- this is true except for lungs - it is the opposite. Oxygen is leaving lung cells (to oxygenate blood) while carbon dioxide is entering lung cells (to be exhaled).

Effects of Extracellular Environment on Cell Mechanisms

-- Outside the cell there is always large fluctuations occurring. In contrast the cell has alterations going on inside the cells. Amplification occurs inside the cell in response to the large fluctuations outside the cells. -- Large EC factors: Heat; Dehydration; Trauma -- Stressors - hypothermia; diabetes; COPD; etc.; Obesity; pH -- Markers = definition -- ** We can't control heat stress (military in full gear, standing in the heat); large external fluctuations = things that you can't control; internal fluctuations and amplification is where you hope that you can get everything under control.

Receptors

-- ______ are proteins

Molarity

-- a mole of a compound can be measured as its molecular weight in grams -- 1M (molar) solution is 1 mole in 1 liter solution -- 1M solution Tris = 121.14 g in 1L ultrapure water

Cell Signaling: Receptors

-- a target cell receives a signal because it has receptor proteins specific to it on the plasma membrane or inside the cell -- lipid soluble (nonpolar) (have a lipid soluble ligand to pass through) (steroid, hormones, thyroid hormone, nitric oxide gas ca penetrate the plasma membrane and interact with receptors inside the cell (b) -- water soluble (large, polar) (must bind extracellular to pass through - extracellular binding domain) (epinephrine, acetylcholine, and insulin bind to receptors on the plasma membrane (a)

Osmosis: clinical case - edema

-- accumulation of fluid in the interstitial fluid (interstitium) -- edema has a multifactorial pathogenesis -- if there is a high solute concentration in the blood (means low water in blood), water will move OUT of tissues and INTO the circulation -- normal solute concentrations within our blood allow water to constantly "fill" or contribute to stable blood volume (albumin typically served this role) -- if solutes happen to get too high and blood volume increases, we typically urinate to remove this excess volume/fluid in an effort to prevent blood pressure from getting too high (due to increased blood volume) -- sometimes there is low solute concentration (which means high water in blood) so water moves OUT of the circulation and INTO tissues - this is why you get observable tissue swelling -- "pitting edema" -- generally, when health is not maintained, vascular integrity is threatened, thereby making blood vessels leaky -- in turn, fluid, electrolytes and proteins move OUT of the circulation and INTO peripheral tissues -- during the clinical condition proteinuria (passing of protein in the urine), edema is commonly observed because you have a state of low "solute" in the blood which means high blood water so water will move DOWN its concentration gradient, into the tissues, thereby causing edema

Integrins

-- are glycoproteins that extend from the intracellular cytoskeleton, through the plasma membrane and bind to the extracellular matrix (serve as an adhesion molecule connecting cells and their extracellular environment) (serve as relay signals between the intracellular and extracellular environment)

Cell Signaling: Signaling Modalities

-- autocrine (ex. pancreatic beta cells can secrete cytokines but they have receptors for cytokines - can be released and then bind and decrease insulin production - is counterproductive and self-destructive)

Receptors

-- can be on cell surface, plasma membrane, or can be intracellular (typically in the nucleus)

Dehydration

-- can increase blood osmolality and therefore osmotic pressure (OP) (because blood becomes more concentrated while total blood volume is reduced) (osmoreceptor neurons in the hypothalamus are stimulated by increased OP...so they shrink due to the increased extracellular osmolality causing: 1) mechanically stimulates them to fire impulses, alerting the person to drink; 2) also promotes water retention so less urination

Active Transport

-- carrier-mediated -- active transport requires energy -- net movement against concentration gradient -- energy (ATP) is provided by carrier proteins (pumps)

Cell Signaling: Paracrine Signaling Type

-- cells within an organ secrete regulatory molecules that diffuse across the extracellular matrix (ECM) to nearby target cells (local, but not touching

Cell Signaling: Gap Junction Type

-- channel proteins between cells that allow the passage of ions and regulatory molecules (very localized) -- cytoplasm must be touching -- intracellular

Aquaporins

-- channels in the membrane during osmosis -- found in the kidneys, eyes, lungs, salivary glands, and the brain

Diffusion of Ions: Required Channels

-- charged ions can pass through ion channels that cross the plasma membrane that may always be open or gated (sodium and potassium; open: diffusion is always occurring; gated: dependent on specific physiological stimuli) -- larger polar molecules can not pass through the membrane by simple diffusion but need special carrier proteins (glucose - glucose transporters, GLUTs) -- like calves (Cav; Kv)

Molality

-- considers the ratio of solute to water -- 1molal (Osm) solutions take the molecular weight i grams dissolved in exactly 1kg (1L) water -- the amount of water never changes, so you can compare solute concentrations to predict the direction of osmosis -- does not depend on the chemistry of the solute, but on how many particles are present in the solution -- dumping 1 mole into a flask already containing 1L of water (so the total can be more than 1L - due to displacement of the water)

Solution

-- consists of a solvent (ex. water) and a solute (ex. molecules dissolved in water) -- molecules in a solution are in a constant state of motion -- if there is a concentration difference between two regions, random motion will establish equilibrium via diffusion

Extracellular Matrix

-- contains protein fibers of collagen and elastin, and a gel-like substance -- protein fibers provide structural support -- collagen contributes to basement membrane -- interstitial fluid is found in this gel-like substance

****Second Messengers: cAMP

-- cyclic adenosine monophosphate (cyclic AMP or cAMP) is a common second messenger -- steps to activate: 1) a polar signaling molecule binds to a cell surface receptor; 2) receptor conformational shape changes which activates adenylate cyclase which generates cAMP from ATP; 3) cAMP concentration increases (signal amplification); 4) cAMP activates other enzymes; 5) cell activities change in response signal = recognition second = drives pathways end result = "downstream" is gene regulation / transcription very redundant, many pathways utilize cAMP: 1) first messengers are signals 2) second messenger mediates functional activity of intracellular mediators / relays; second messenger drives intracellular mediators; secons messengers always drive amplification 3) all of the above must occur for a response

Net Diffusion

-- due to random movement -- direction is from high to low solute concentration

Intracellular Mediators

-- enzymes, proteins -- they mediate signal transduction from extracellular all the way down to the nucleus -- ***these pathways work like metabolic pathways in the sense if a process goes wrong the next process won't work either

Isotonic

-- equal tension so osmosis will not occur -- equal inside and outside of rbc

Cell Signaling: Integration

-- estimated that the 200 different cell types in the human body may have as many as 30,000 different types of receptors

Cell Signaling: Endocrine Signaling Type

-- glands secrete hormones into the bloodstream (therefore, can cover long distances to reach target cells) -- extracellular

Molarity and Osmosis

-- glucose has a molecular weight of 180g/mole. To make a 1M solution of glucose...dissolve 180g glucose in 1L water -- NaCl has a molecular weight of 58.5g/mole. To make a 1M solution of NaCl...dissolve 58.5g NaCl in 1L water

Tonicity

-- how does a solution affect osmosis? -- higher solute concentrations increase osmotic pressure -- describes the effect a solution has on the osmotic movement of water (isotonic, isosmotic, hypo-osmotic, hypotonic, hypertonic) -- plasma has the same osmolality as a 0.3m glucose or a 0.15m NaCl solution (isosmotic to plasma) -- takes into account the permeability of the membrane to the solutes (if the solutes can cross the membrane, the tonicity will change) -- solutions with a lower solute concentration than the cell are hypo-osmotic and hypotonic (if the solutes are osmotically active) (will pull water into the cell causing the cell to swell and could lyse...hemolysis if blood cells) -- solutions with a higher solute concentration than the cell are hyper-osmotic and hypertonic (if the solutes are osmotically active) (will pull water out of the cell causing the cell to shrivel up and could crenate - become notched or scallop-edged)

Extracellular Environment

-- includes everything located outside the cells (nutrients, oxygen, metabolic waste, signaling molecules, hormones, steroids, drugs) -- cells receive NOURISHMENTS from and relase WASTES into the extracellular environment -- cells COMMUNICATE with each other by SECRETING CHEMICAL REGULATORS into the extracellular environment -- all of this occurs ACROSS THE PLASMA MEMBRANE

Salt Intake

-- increases plasma osmolality and OP (osmotic pressure) too -- you get thirsty because the osmoreceptor neurons are shrinking (due to increased osmotic pressure) so this in turn stimulates you to drink as well as ADH release so the kidneys will retain water -- this ends up diluting the salt in an effort to return extracellular sodium concentrations to normal -- but you end up with a higher blood volume due to drinking and water retention

Integrins: Physiological Significance Example

-- integrins on monocytes bind to vascular adhesion molecules on the endothelium in an effort to promote adhesion and migration into tissues (diapedesis) -- starts out as a monocyte and invades the tissue and changes into macrophage -- diapedesis = the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation -- goes from the blood stream and enters the tissue.

Molarity

-- is not useful for a discussion of osmosis, since the solute concentration is different depending on the solute -- example: more water is used to make the 1M solution of NaCl (because you are adding almost 3-fold less solute) -- dumping in 1 mole into a flask and bringing it up to 1L total volume (so total volume will always be 1L)

G-Protein-Coupled Receptor (GPCR)

-- ligand = extracellular binding domain -- extracellular = n-terminus -- heterotrimeric g-protein = c-terminus...

Cell Signaling: Principle Concept - Reception

-- lock and key -- physiological significance: it offers specificity (to control physiological responses

Water Intake

-- lowers plasma osmolality and osmotic pressure -- kidneys play a critical role

Cell Signaling: Nuclear Receptors

-- many lipid-soluble regulatory molecules act as transcription factors 1) lipid-soluble hormone diffuses into cell 2) activated receptor hormone complex alters gene expression 3) newly formed mRNA directs synthesis of specific proteins on ribosomes 4) new proteins alter cell's activity

Cell Signaling: Synaptic Signaling Type

-- neurons release neurotransmitters into synaptic cleft to target cells (other neurons or target cells in organs) (axons innervate target cell or organ) -- ex. kidney releases neurotransmitter and kidney cell with receptor will bind neurotransmitter

Passive Transport

-- noncarrier-mediated (high to low) -- net movement down concentation gradient so no energy required -- simple diffusion of lipid-soluble (nonpolar) molecules -- simple diffusion of ions through ion channels -- simple diffusion of water through aquaportin channels ---> osmosis

Cell Signaling: Signal Amplification

-- one messenger molecule leads to phosphorylation of millions of proteins 1) one messenger binds to one receptor 2) several G proteins are activated 3) each G protein activates an adenylate cyclase 4) each adenylate cyclase generates hundreds of cAMP molecules 5) each cAMP activates a protein kinase A 6) each protein kinase A phosphorylates hundreds of proteins

Hypotonic

-- osmotically active solutes at a lower concentration than the other solution (water into rbc causing it to expand and possibly burst) -- pure water is hypotonic because it has essentially no solutes at all while cells do - they require ions, proteins, all kinds of things to function

Purpose of Cell Signaling Components

-- overall ______ is to take the ECF signal with an end result of creating a physiological response

Plasma Membrane Transport: Bidirectional

-- plasma membrane is semi-permeable -- it allows some molecules to cross but not others -- can move through: oxygen, carbon dioxide, and other small, nonpolar molecules; some water molecules (fatty acids; vitamins - A, D, E, K; steroids) -- can NOT move through: glucose and other large, polar, water-soluble molecules; ions (e.g. H+, Na+, K+, Ca++, Cl-); water molecules (polysacharides, amino acids, glucose, nucleic acids)

G-Proteins: Receptor / G-Protein / Effector

-- receptor = cell surface or membrane; pm; c-terminus -- g-protein (GPCR) -- effector (IC)

G-Proteins: Three Protein Subunits

-- receptor proteins that bind to a signal and enzyme proteins that produce a second messenger are rarely localized together within the plasma membrane (they require something to shuttle between them) (____ are made up of 3 subunits - alpha, beta, and gamma; dictate the activity of cAMP) (one subunit dissociates when a signal molecule binds to the receptor and travels to the enzyme or ion channel) -- image is and activated enzyme (adenylate cyclase - makes cAMP - intracellular)

Isosmotic

-- same osmolality (1 osm unit : 1 osm unit) -- a solution may be isosmotic but not isotonic (depends on the permeability of the membrane)

Cell Signaling: Principle Concept - Transduction

-- second messengers and intracellular messengers / mediators -- they drive the response -- must have a cellular response to drive the physiological response

Osmolality (Osm)

-- solutes that DO dissociate -- electrolytes that dissociate in water have to be assessed differently -- NaCl dissociates into Na+ and Cl- in water and must be counted as separate paticles (NaCl ---> Na+(aq) + Cl-(aq) (aq = aqueous) -- a 1molal NaCl solution would acutally be a 12 Osm solution (because 1 Osm unit for sodium + 1 Osm unit for chloride) -- if inside the semipermeable sack contains 1 molal glucose (which is 1 Osm unit) and the membrane is not permeable to glucose, water will move outside. Because NaCl will dissociate, generating 2 Osm units total. Thus the EC solution is hypertonic. -- upon completion of osmosis, the osmolality of the solution inside the sack and outside in the beaker is equal. -- a) High mosmolality high sol. (2); low water; high OP; high OSM (make sure to see what the membrane is permeable to, and then which direction is water moving)

Osmolality (Osm)

-- solutes that do not dissociate -- total molality of a solution when you combine all of the molecules within it -- a 360g (2 molality) glucose solution compared to a solution containing 180g glucose (1 molality) + 180g fructose (1 molality) would have the same osmolality...why? -- these are both 2 Osm solutions: glucose solution = 2 Osm; glucose + fructose solution = 1 + 1 = 2 Osm -- Each molal is equivalent to 1 Osm unit. Such that 2 molals of glucose equates to a 2 Osm solution inside the membrane sack -- the "extracellular" environment contains a solution of 1 molal glucose (1 Osm unit) and 1 molal of fructose (1 Osm unit) such that 1 Osm unit + 1Osm unit = 2 total Osm units. Thus there is no net movement of water between the membrane sack and extracellular environment because the total number of solute particles is equal.

Extracellular Factor (ECF)

-- substrate or ligand (can be growth factor, hormones, cytokine)

Mean Diffusion Time

-- the average time it takes for a solute to diffuse (less distance, faster time)

Osmotic Pressure: Outside Forces

-- the force surrounding a cell required to stop osmosis...the pressure needed to stop osmosis -- a higher solute (low water) concentration would require a higher osmotic pressure (this means water concentration is low) (so the cell would have to really resist allowing its water to flow outwards - high inside to low outside - thereby preventing shrinkage) -- pure water has an osmotic pressure of zero

Diffusion Rate

-- the steeper the concentration gradient the faster the diffusion rate -- regardless of what side has highest/lowest solute concentration -- increasing temperature slightly can increase it...why? because is makes molecules move faster -- size matters -- permeability of membrane -- surface area of membrane (larger, increased rate)

Nucleus

-- transduction occurs to drive a physiological response -- genes must be transcribed specifically to that physiological response that needs to be generated

Extracellular Environment: function of the blood

-- transports: 1) oxygen from lungs to periphery...why? To feed the body; 2) carbon dioxide (waste) from body to lungs for removal (by what mechanism?)...why? exhaling; 3) nutrients derived from food in the intestine to body cells; 4) nutrients between organs (glucose from liver to brain; lactic acid from muscles to the liver...why? It goes there to be converted to pyruvate then to G-6-P which can enter glycogenesis or gluconeogenesis); 5) metabolic wastes from body cells to the liver and kidneys for elimination...why the liver and kidneys? filtration of blood; 6) regulatory hormones released from endocrine organs to cells within their target organs

Body Fluids

-- two (2) compartments (intracellular and extracellular) -- intracellular (cytoplasm): 67% of our water is within cells -- extracellular: 33% (20% blood plasma; 80% tissue fluid or interstitial fluid) (found in the gel-like extracellular matrix) (connects the intracellular compartment with the blood plasma) (formed continuously recycles from and to blood plasma)

What are the different ways in which signals can be integrated?

1) one receptor activates multiple pathways 2) different receptors activate the same pathway 3) different receptors activate different pathways; one pathway affects the other

***G-Proteins: Types of G-Alpha Subunits

-- type dictates signaling cascade -- GPCRs can mainly be sub-classified by g-protein type, i.e. g-alpha(s), g-alpha(i), g-alpha(q) -- the amount of decrease in cAMP levels by gi-coupled receptor activation depends on the basal level of cAMP present within the cells; often, the effects of this inhibition are more easily observed when a specific agent, such as forskolin, is used to activate adenylate cyclase 1) subunit activation: g-alpha(i) or (Gi); effector + signal transduction: --> inhibition of Adenylate Cyclase (AC) --> decrease in intracellular cAMP concentration; second messengers: cAMP 2) subunit activation: g-alpha(s) or (Gs); effector + signal transduction: --> stimulation of Adenylate Cyclase (AC), --> increase in intracellular cAMP concentration 3) subunit activation: g-alpha(q) or (Gq); effector + signal transduction: --> Phospholipase C (PLC) induction and triggers the inositol phosphate cascade --> transient increase in intracellular IP3 concentration and subsequent calcium release from the endoplasmic reticulum (ER)

Osmosis

-- water molecules do not carry a charge, so they can pass through the plasma membrane slowly (aided by aquaporins) -- must be a solute concentration difference on either side of a membrane permeable to water -- the membrane must be impermeable to the solute...why? so that you can... -- or the concentration difference will not be maintained (solutes that cannot cross and permit osmosis are called osmotically active) -- water moves down its concentration gradient (from low solute concentration to high solute concentration)

***Second Messengers: The cAMP + Ca++ Pathways

-- when a signal molecule such as epinephrine binds to a cell surface receptor protein, it activates a g-protein on the inside of the cell -- the g-protein then stimulates adenylyl cyclase to produce large amounts of cyclic AMP within the cell -- the cyclic AMP then binds to and activates a target protein such as alpha-kinase, which adds phosphates to specific proteins in the cell -- the effect of this phosphorylation depends on the identity of the cell and the proteins that are phosphorylated -- calcium ions also serve as second messengers. In response to a signal molecule from other cells, the cell surface receptor protein activates a g-protein, which in turn activates the enzyme phospholipase C -- this enzyme catalyzes the production of inositol triphosphate, which diffuses through the cytoplasm to the endoplasmic reticulum -- the inositol triphosphate binds to and opens the calcium channels, allowing calcium ions to flow from the endoplasmic reticulum into the cytoplasm -- the calcium ions trigger proteins sensitive to calcium to initiate a variety of activities OR a) Channel-Linked Receptors: 1) signal binds; 2) channel opens; 3) ions flow across membrane b) Enzyme-Linked Receptors: 1) signal binds; 2) enzyme activated; 3) enzyme generates product c) G-Protein-Coupled Receptors: 1) signal binds; 2) g-protein binds; 3) g-protein activated d) Intracellular Receptors: 1) signal binds; 2) activated receptor regulates transcription

Ligand-gated ion channels

1) neurotransmitter (ligand) binds 2) channel opens 3) ions flow across membrane

Cell Signaling: Principle Concept

1) reception 2) signal transduction 3) response

Diffusion of a Solute

1) a lump of sugar is dropped into a beaker of water 2) sugar molecules begin to break off from the lump 3) more and more sugar molecules move away and randomly bounce around 4) eventually, all of the sugar molecules become evenly distributed throughout the water

Function of Integrins

1) adhesion molecule - connecting cells and the extracellular matrix 2) relay signals - between intracellular and extracellular environment 3) confer polarity to cells - such that one side is functionally different from the other (apical vs. basal) 4) contribute to cell adhesion in tissues 5) contribute to cell motility 6) impact cell proliferation (growth, increasing number) 7) bind to secreted regulatory chemicals (signal transduction) (primarily mediate growth factor binding to their receptors)

Factors that can impact blood osmolality

1) dehydration 2) salt intake 3) water intake

Cell Signaling: Four Types

1) gap junctions 2) paracrine signaling 3) synaptic signaling 4) endocrine signaling

Steps in the G-Protein Coupled Receptor Pathway:

1) ligand binds to receptor 2) conformational change in receptor 3) G-protein alpha subunit dissociates from beta/gamma complex (g-alpha is now activated) 4) alpha subunit moves through membrane and binds to adenylate cyclase (or an ion channel) 5) alpha subunit hydrolyzes GTP into GDP causing alpha / beta / gamma to regroup and move back to the receptor protein (g-alpha is now deactivated)

G-protein-coupled receptors

1) nerotransmitter (ligand) binds 2) G-protein is activated 3) G-protein subunits or intracellular messengers modulate ion channels 4) ion channel opens 5) ions flow across membrane

Signal Transduction Steps:

1) recognition - receptor is recognizing the ligand (signal) 2) signal transduction - 2nd messenger activates the intracellular mediators (also known as the relays); so important because...amplification (amplifying the signal) 3) regulating gene expression - physiological outcome is physiological response (ex. promoting blood clotting, immune response, response to MI) -- heterotrimeric g-protein (alpha-beta-alpha: GDP inactive)(c-terminus...) -- colocalization = coming together of alpha and proteins (mixing of "red" and "blue" = "purple")

G-Protein Overview:

1) resting state: receptor is not bound to ligand; g-alpha subunit is bound to GDP and associated with g-beta-gamma 2) ligand binds receptor; the receptor binds a g-protein; g-alpha releases GDP and acquires GTP 3) g-alpha and g-beta-gamma subunits separate 4) g-protein subunits activate or inhibit target proteins, initiating signal transduction events 5) the g-alpha subunit hydrolyzes its bound GTP to GDP, becoming inactive 6) subunits recombine to form an inactive g-protein

d) Increased rate of diffusion of sodium into the cells.

A drug is known to cause a change in the resting membrane potential of renal tubular epithelial cells from -60 mV to -50 mV. Which of the following findings could be the cause? a) Decreased rate of diffusion of sodium into the cells. b) Decreased rate of diffusion of potassium into the cells. c) Increased rate of diffusion of potassium into the cells. d) Increased rate of diffusion of sodium into the cells.

c) Activation of cAMP or Cgmp.

A neurotransmitter binds to a G-protein-linked receptor and activates a specific second messenger in its target cell. Which of the following represents an activity performed by the activated second messenger? a) Inactivation of enzymes that initiate biochemical reactions. b) Direct activation of gene transcription. c) Activation of cAMP or Cgmp. d) Closure of a membrane channel for sodium or potassium ion.

d) receptor → G protein → second messenger → biological response

A typical flow of information in a signal transduction pathway would be: a) hormone → second messenger → receptor → biological response b) hormone → second messenger → receptor → biological response c) receptor → second messenger → biological response → G protein d) receptor → G protein → second messenger → biological response

b) Decreased transport.

An amino acid is transported into cells via secondary active transport. Administration of a drug that blocks the activity of the Na/K ATP-ase would have what effect on the transportation of this amino acid into the cell? a) Increased transport. b) Decreased transport. c) No change in transport.

Interstitial fluid (tissue fluid)

Approximately 80% of the extracellular fluid is outside the vascular system and is called _________.

Central Inflammation

Can end up with ____ because of the integrity of the tight junctions and the leaky blood vessels and the blood brain barrier.

The higher extracellular solute concentration will mean that it contains low water, thereby drawing OUT water from cwerebellar tissue and reducing swelling.

Cerebral Edema (tonicity; clinical application) -- hypertonic solutions like mannitol are commonly used to treat cerebral edema, a significant cause of mortality in patients suffering from stroke or head trauma Why?

The membrane potential is the difference in charge across the membrane. Differences in charge, or differences in potential, are measured in units of voltage. Because voltage is a measure of potential difference, two electrodes - one placed inside the cell and one placed in the extracellular environment - are needed. A device that functions as a voltmeter can then measure the potential difference across the membrane between these two electrodes.

Define membrane potential and explain how it is measured.

Isotonic solutions have the same osmolality and osmotic pressure. When one solution is referred to as isotonic, it is because it has the same osmolality and osmotic pressure has plasma. Hypotonic solutions have a lower, and hypertonic solutions have a higher, osmolality and osmotic pressure. Tissue cells exposed to hypotonic solutions will gain water and those exposed to hypertonic solutions will lose water, whereas those exposed to isotonic solutions will do neither. That is why 5% dextrose and normal saline, which are isotonic solutions, are used in hospitals.

Define the terms isotonic, hypotonic, and hypertonic, and explain why hospitals use 5% dextrose and normal saline as intravenous infusions.

Osmosis is the net movement of water by diffusion across the plasma membrane. Osmolality is the total molal concentrations of solutes in a solution, and the osmotic pressure of a solution refers to the pressure needed to stop osmosis into the solution. In order for osmosis to occur, a membrane must separate two solutions that contain different osmolalities and the membrane must be more permeable to water than to at least one of the solutes in these solutions.

Define the terms osmosis, osmolality, and osmotic pressure, and state the conditions that are needed for osmosis to occur.

Active transport is an ATP-requiring process that moves substances across the plasma membrane against their concentration gradients. Primary active transport depends on carrier proteins called "pumps" that are powered by the hydrolysis of ATP. These pumps move substances from lower to higher concentrations, accentuating concentration differences. These differences, maintained by primary active transport, could be used to power secondary active transport in which a different carrier moves a different substance across the membrane. In facilitated diffusion, movement of a substance is always down its concentration gradient and, though a carrier is required, ATP is not needed either directly or indirectly.

Describe active transport, including primary and secondary active transport in your description. Explain how active transport differs from facilitated diffusion.

The extracellular matrix of ordinary connective tissues consists of a ground substance made of water, glycoproteins, and proteoglycans, and protein fibers of collagen and elastin. Matrix metalloproteinase enzymes can degrade the extracellular matrix. These enzymes aid normal processes such as tissue remodeling and the movement of cells through the matrix, but can cause tissue destruction in pathological cases.

Describe the composition of the extracellular matrix and explain the importance of the matrix metalloproteinases.

About 67% of the total body water is in the intracellular compartment. Of the fluid in the extracellular compartment, about 20% is in the blood plasma and 80% is tissue, or interstitial, fluid.

Describe the distribution of fluid in the body.

An equilibrium potential is the membrane potential required to stabilize the normal difference in concentration of an ion on the two sides of the plasma membrane if the membrane is permeable to it. The equilibrium potential for K+ is -90 mV, and the equilibrium potential for Na+ is +60 mV. The actual membrane potential is closer to the K+ equilibrium potential because the resting membrane is more permeable to it. If the membrane becomes more permeable to a particular ion, the membrane potential is moved towards that ion's equilibrium potential.

Describe the potassium and sodium equilibrium potentials.

These pumps accentuate the difference in concentration of Na+ and K+ across the membrane by pumping three Na+ out of the cell for every two K+ they pump into the cell. This is needed for at least three functions: (1) the steep Na+ gradient produced by the pumps is needed for secondary active transport (of glucose, for example); (2) these pumps contribute to the potential difference across the plasma membrane, which is required for the electrochemical impulses produced by neurons and muscle cells; and (3) the extrusion of Na+ is required for osmotic reasons, to prevent the undue osmosis of water into cells.

Discuss the physiological significance of the Na+/K+ pumps.

Synaptic regulation occurs by means of neurotransmitter chemicals released from presynaptic axon terminals that diffuse a short distance across a synaptic gap to a postsynaptic cell. Endocrine regulation occurs via hormones secreted by endocrine glands into the blood, which carries the hormones throughout the body to distant target cells. Paracrine regulation occurs by means of regulatory chemicals released by cells of an organ that diffuse to neighboring target cells in the same organ.

Distinguish between synaptic, endocrine, and paracrine regulation.

The student should draw a figure similar to fig. 6.15. This figure illustrates saturation, where the transport rate reaches a plateau at a particular concentration of the diffusing substance - beyond this point, an increase in concentration does not produce an increase in transport rate. The graph also illustrates competition, because two like substances (X and Y in the figure), when present together, decrease the transport rate of each other by competing for carriers.

Draw a figure that illustrates two of the characteristics of carrier-mediated transport and explain how this type of movement differs from simple diffusion.

b) Na+ ions enter the cell along a concentration gradient and along an electrical gradient.

During the resting membrane potential a) K+ ions leave the cell against a concentration gradient but along an electrical gradient. b) Na+ ions enter the cell along a concentration gradient and along an electrical gradient. c) Na+ ions enter the cell along a concentration gradient but against an electrical gradient. d) K+ ions leave the cell along a concentration gradient and along an electrical gradient.

Osmoreceptor neurons in the hypothalamus lose water when the plasma osmolality increases. This stimulates them, promoting a sense of thirst. Also, these neurons stimulate the posterior pituitary gland to secrete antidiuretic hormone (ADH), which stimulates the kidneys to retain water. Thus, in dehydration, we drink more and urinate less, maintaining homeostasis of plasma osmolality.

Explain how the body detects changes in the osmolality of plasma and describe the regulatory mechanisms by which a proper range of plasma osmolality is maintained.

The resting membrane potential is close to the K+ equilibrium potential because the resting membrane is more permeable to K+ than to Na+. It is slightly less negative (about -70 mV compared to -90 mV) because the plasma membrane does allow some Na+ to enter the cell through leakage channels. Because of this, the resting membrane potential does not prevent a new efflux of K+. The slow inward movement of Na+ and outward movement of K+ are countered by the constant activity of Na+/K+ pumps.

Explain the relationship of the resting membrane potential to the two equilibrium potentials.

Simple diffusion refers to membrane transport in which the ions or molecules pass through the plasma membrane down their concentration gradients without requiring specific carrier proteins. Diffusion rate depends on the steepness of the concentration gradient (the difference in concentration between one side and another of the plasma membrane), the surface area of the membrane involved, the permeability of the membrane to the diffusing substance, and on the temperature.

Explain what is meant by simple diffusion and list the factors that influence the diffusion rate.

Second Messengers: Membrane Receptors -- polar (water soluble) or large signal molecules bind to receptors on the cell surface -- signal pathway mediator proteins called second messengers integrate the extracellular signal and intracellular-mediated physiological outcome 1) can be ions (typically calcium) (enter the cell through ion channels); 2) can be cytoplasmic proteins

How does a ligand that binds to a cell surface receptor exert its effects inside the cell?

-- osmoreceptor neurons in the hypothalamus stimulate a tract of neurons that terminate in the posterior pituitary ---> causes the posterior pituitary to release antidiuretic hormone / vasopressin (ADH) into the circulation ---> ADH acts on the kidneys to promote water retension such that urination is minimized -- this maintains plasma concentration (osmolality) and blood volume

How does dehydration lead to water retention? (regulation of osmolality)

Receptor proteins for water-soluble regulatory molecules are generally located on the plasma membrane surface, facing the extracellular environment. Interactions between the regulatory molecules and these receptors then generate second messengers that act within the cell to effect the regulation. Lipid-soluble regulatory molecules can cross the plasma membrane and interact with receptor proteins within the cell, either in the cytoplasm or the nucleus.

Identify the location of the receptor proteins for different regulatory molecules.

a) he movement of Na+ out of a cell

If a poison such as cyanide stopped the production of ATP, which of the following transport processes would cease? a) he movement of Na+ out of a cell b) Osmosis c) The movement of K+ out of a cell d) All of these

Because the membrane of the RBC is permeable to urea. Urea can cross into the RBCs thereby increasing the solute concentration inside the cell (meaning low water inside the cell) so water moves down its gradient into the RBC causing it to lyse.

If you place RBCs (0.3m) in a 0.3m solution of urea, the solution is isosmotic to the RBCs but the tonicity will not be isotonic. Why?

b) moves closer to 0 millivolts

In hyperkalemia, the resting membrane potential a) moves farther from 0 millivolts b) moves closer to 0 millivolts c) remains unaffected

Blood Plasma

Interstitial fluid is continuously formed from and returned to the ________.

Passive transport includes all of the non-carrier-mediated processes involving the simple diffusion of ions through membrane channels, nonpolar molecules through the lipid bilayer of the plasma membrane, and water through aquaporin channels, as well as the carrier-mediated process of facilitated diffusion. Passive transport does not require metabolic energy, whereas the membrane carriers of active transport directly or indirectly require ATP to move molecules and ions against their concentration gradients.

List the subcategories of passive transport and distinguish between passive transport and active transport.

Facilitated diffusion, which is diffusion down the concentration gradient requiring the action of carriers, differs from simple diffusion (not involving carriers) in its specificity for the diffusing substance, competition between like substances for a particular carrier, and the ability of a carrier to reach saturation, where the transport rate levels off when the diffusing substance reaches a certain concentration.

List the three characteristics of facilitated diffusion that distinguish it from simple diffusion.

1. d; 2. c; 3. a; 4. b

Match the concentrations of Na+ and K+ inside and outside the cell membrane: 1) K+ outside 2) K+ inside 3) Na+ inside 4) Na+ outside a) 12 mM b) 145 mM c) 150 mM d) 5 mM

c) Facilitated diffusion.

Molecule X is a large protein, present in higher concentration in the extracellular fluid (ECF) than in the intracellular fluid (ICF). Which of the following is the most likely means of getting molecule X from the ECF to the ICF? a) Primary active transport. b) Secondary active transport. c) Facilitated diffusion. d) Ligand-Gated ion channel.

b) 300 mOsm

Plasma has an osmolality of about 300 mOsm. The osmolality of isotonic saline is equal to a) 150 mOsm b) 300 mOsm c) 600 mOsm d) none of these

c) a hypertonic solution

Red blood cells crenate in a) a hypotonic solution b) an isotonic solution c) a hypertonic solution

1) directly from one cell to another (because their plasma membranes are very close together and their cytoplasm is coupled) (continuous via gap junctions) (ions and regulatory molecules can diffuse through) 2) released into extracellular environment via a) paracrine; b) synaptic; and c) endocrine (most signals are through these mechanisms

Signals between cells can travel via what methods?

c) Hyposmotic; Isotonic.

Solution A contains 100 mM CaCl2 and 50 mM glucose. Solution B contains 175 mM NaCl. These solutions are seperated by a membrane that is permeable to all solutes except glucose. Which of the following best describes solution A in comparison to solution B? a) Isosmotic; Hypertonic. b) Isosmotic; Isotonic. c) Hyposmotic; Isotonic. d) Hyperosmotic; Isotonic. e) Hyposmotic; Hypotonic.

Extracellular Matrix: Clinical Application

Study that she was involved in... -- involved in the pathogenesis of degenerative joint disease -- required for normal tissue remodeling and macrophase migration during infection -- but if overexpressed then it destroys cartilage -- MMPs are required normally for tissue remodeling (wear and tear). Can run rampant and can break down tissue.

d) all of these

Suppose that gated ion channels for Na+ or Ca2+ opened in the plasma membrane of a muscle cell. The membrane potential of that cell would a) move toward the equilibrium potential for that ion b) become less negative than the resting membrane potential c) move farther away from the potassium equilibrium potential d) all of these

Lactic Acid Dehydrogenase (LDH)

The enzyme responsible for converting lactic acid to pyruvate is ____?

Extracellular Matrix; Protein Fibers; Ground Substance

The extracellular material of the connective tissue is called ________ which is made of ______ and ______.

c) slightly more positive than the equilibrium potential of potassium ion.

The membrane potential of most neurons at rest is a) equal to the equilibrium potential of sodium ion. b) slightly more negative than the equilibrium potential of potassium ion. c) slightly more positive than the equilibrium potential of potassium ion. d) equal to the equilibrium potential of potassium e) slightly more positive than the equilibrium potential of sodium ion.

a) K+

The most important diffusible ion in the establishment of the membrane potential is a) K+ b) Na+ c) Ca2+ d) Cl-

c) simple diffusion through membrane channels

The movement of water across a plasma membrane occurs by a) an active transport water pump. b) a facilitated diffusion carrier. c) simple diffusion through membrane channels. d) all of these.

a) Facilitated diffusion.

The rate of absorption of a drug taken orally is found to increase as the dose is increased up to a point where further increase in dose has no further increase in the rate of absorption. Which of the following processes best describes the drug absorption? a) Facilitated diffusion. b) Primary active transport. c) Simple diffusion. d) Secondary active transport.

c) somewhat less negative than the potassium potassium equilibrium potential

The resting membrane potential of a neuron or muscle cell is a) equal to the potassium equilibrium potential b) equal to the sodium equilibrium potential c) somewhat less negative than the potassium potassium equilibrium potential d) somewhat more positive than the sodium equilibrium potential e) not changed by stimulation

Paracrine

The use of a chemical messenger to transfer information from one cell type to another cell type within a single tissue is referred to as _____ signaling.

b) Potassium.

This ion is primarily responsible for maintaining the resting membrane potential of excitable cells. a) Sodium. b) Potassium. c) Chloride. d) Protein. e) Calcium.

True

True or False Higher solute concentrations increases osmotic pressure?

True

True or False Is simple diffusion down concentration gradient?

True

True or False? Cells communicate with each other using chemical signals?

These pumps are constantly active to maintain the concentrations of Na+ and K+ on the two sides of the plasma membrane. This action is required because the resting membrane potential is slightly less negative than the K+ equilibrium potential, and far more negative than the Na+ equilibrium potential. The pumps also contribute to the membrane potential because they pump out 3 Na+ for every 2 K+ they pump into the cell.

What role do the Na+/K+ pumps play in establishing the resting membrane potential?

a) Primary active transport.

Which of the following has a direct requirement for ATP in order to function properly? a) Primary active transport. b) Secondary active transport. c) Facilitated diffusion. d) Simple diffusion. e) Osmosis.

d) Potassium.

Which of the following may be transported from the intracellular fluid to the extra-cellular fluid without using cellular energy? a) Proteins. b) Amino acids. c) Sodium. d) Potassium.

d) Pinocytosis.

Which of the following modes of transport is most likely to experience the phenomenon of saturation? a) diffusion. b) Facilitated diffusion. c) Primary active transport. d) Pinocytosis.

a) they are needed to mediate the action of nonpolar regulatory molecules

Which of the following questions regarding second messengers is false? a) they are needed to mediate the action of nonpolar regulatory molecules b) they are released from the plasma membrane into the cytoplasm of cells c) they are produced in response to the binding of regulatory molecules to receptors in the plasma membrane d) they produce the intracellular actions of polar regulatory molecules

a) The more soluble X is in nonpolar solvents, the more rapidly X diffuses across the membrane.

Which of the following statements about diffusion of substance X across a plasma membrane is true? a) The more soluble X is in nonpolar solvents, the more rapidly X diffuses across the membrane. b) The smaller the molecular weight of X is, the slower its diffusion. c) If X is water, its rate of diffusion across membranes is low. d) If X is water soluble, its diffusion across membranes will be fast even when its molecular weight is large.

a) are components of the extracellular matrix.

Which of the following statements is not true of integrins? They a) are components of the extracellular matrix. b) serve as adhesion molecules. c) relay signals between the cell and the extracellular matrix. d) impart polarity to the cell.

d) Use magnesium ion as a cofactor.

Which of the following statements is not true of matrix metalloproteinases? a) Important in tissue remodeling. b) Assist in the migration of phagocytic cells during the fight against infection. c) Secreted in their inactive form and activated in the extracellular matrix. d) Use magnesium ion as a cofactor.

a) On activation, the alpha subunit separates from beta and gamma subunits.

Which of the following statements is true about G proteins? a) On activation, the alpha subunit separates from beta and gamma subunits. b) Activation involves binding GDP. c) Interaction with an agonist promotes inactivation of a G protein. d) Activation is reversed when GTP is bound.

e) A and B only

Which of the following will result in an increase in diffusion rate across the membrane? a) Higher concentration gradient. b) Reduced membrane thickness. c) Less surface area. d) All of the above e) A and B only

b) movement of Na+ and K+ through the action of the Na+ / K+ pumps

Which of these is not an example of cotransport? a) movement of glucose and Na+ through the apical epithelial membrane im the intestinal epithelium b) movement of Na+ and K+ through the action of the Na+ / K+ pumps c) Movement of Na+ and glucose across the kidney tubules d) movement of Na+ into a cell while Ca2+ moves out

d) the pumps are constantly active in all cells

Which of these statements about the Na+ / K+ pump is true? a) Na+ is actively transported into the cell b) K+ is actively transported out of the cell c) an equal number of Na+ and K+ ions are transorted with each cylce of the pump d) the pumps are constantly active in all cells

b) Carrier proteins in the cell membrane are required for this transport

Which of these statements about the facilitated diffusion of glucose is true? a) There is a net movement from the region of lower to the region of higher concentration. b) Carrier proteins in the cell membrane are required for this transport. c) This transport requires energy obtained from ATP. d) It is an example of cotransport.

d) all of these are true

Which of these statements comparing a 0.5 m NaCl solution and a 1.0 m glucose solution is true? a) they have the same osmolality b) they have the same osmotic pressure c) they are isotonic to each other d) all of these are true

a) it can occur as a result of dehydration

Which of these statements regarding an increase in blood osmolality is true? a) it can occur as a result of dehydration b) it causes a decrease in blood osmotic pressure c) it is accompanied by a decrease in ADH secretion d) all of these are true

b) it is used for cellular uptake of blood glucose

Which os these statements about carrier-mediated facilitated diffusion is true? a) it uses cellular ATP b) it is used for cellular uptake of blood glucose c) it is a form of active transport d) none of these are true

antiport

moving two molecules in opposite direction

symport

moving two molecules in the same direction

Cell Signaling

signals = ligands