Cell Biology Chapter 12: Membrane Transport I

What 2 characteristics of an ion or molecule does a CHANNEL discriminate against? How about a transporter?

-CHANNELS determine whether an ion or molecule can pass through based on SIZE and ELECTRIC CHARGE. *Channels transfer solutes at a MUCH GREATER RATE than transporters. -TRANSPORTERS ONLY transfer molecules or ions that FIT into SPECIFIC BINDING SITES on the protein.

What are myelin sheaths and what do they do?

A MYELIN SHEATH is an "insulation" feature, enclosing the axon of a neuron. *They INCREASE the RATE of NERVE CONDUCTION.

What is multiple sclerosis?

An AUTOIMMUNE DISORDER in which the immune system DESTROYS MYELIN SHEATHS.

What are antimicrobial peptides (AMPS)? Why are they produced? What charges do they carry? Are they amphiphilic (or amphipathic)? What is a defining feature of AMPs and how does this affect intracellular processes?

Antimicrobial peptides are SMALL MOLECULAR WEIGHT PROTEINS with BROAD SPECTRUM antimicrobial activity against bacteria, viruses, and fungi. -They are produced as part of an INNATE IMMUNE RESPONSE. *Usually, they are positively charged and amphiphilic (or amphipathic); having both a hydrophobic and hydrophilic side allos them to be soluble in water environments, as well as enter lipid-rich membranes. *A defining feature of AMPs is that they ASSOCIATE with MEMBRANES. This can be a problem though because not all of them make the membrane permeable; some translocate across the membrane and INTERFERE with INTRACELLULAR PROCESSES.

Briefly explain why the Na+ pump keeps the concentration of Na+ low and K+ high inside of the cell. How many ions of Na+ and K+ are pumped out/in to the cell for every 1 ATP hydrolyzed?

The pump keeps the Na+ concentration in the cytosol LOW and the K+ concentration in the cytosol HIGH. *For every ATP hydrolyzed inside the cell via the electrogenic pump, 3 Na+ ions are moved OUT and 2 K+ are moved IN. -The difference in concentration of each ion (on either side of the membrane) contributes to its own electrochemical gradient (stored potential energy).

What are synapses?

They are SPECIALIZED JUNCTIONS that allow signals to be transmitted from one cell to another; also where neurons connect to their target cells (usually other neurons or muscle cells).

Briefly describe how the glucose transporter passively mediates glucose across the plasma membrane.

The glucose transporter is a membrane protein in which transports glucose inside or outside of the cell. Since glucose is an UNCHARGED molecule, the direction in which it is transported is SOLEY determined by its concentration gradient. Additionally, the glucose transporter protein (which crosses the membrane at least 12 times) can adopt several conformations based on cellular needs; the glucose transporter switches between exposing binding sites for glucose to the exterior of the cell or exposing the sites to the cell interior. *If glucose is plentiful OUTSIDE of cells, the glucose transporter protein will adopt the conformation to allow binding of the glucose to the receptor sites of the glucose transporter, which will then change conformations and bring the bound sugar inward, releasing it into the cytosol. *If glucose is low OUTSIDE of cells, the HORMONE GLUCAGON stimulates LIVER CELLS to produce large amounts of glucose via the BREAKDOWN of GLYCOGEN. When the glucose is higher INSIDE of CELLS compared to the outside, the glucose transporter protein changes conformation again to allow the transportation of glucose OUTSIDE of cells. *Transporters are HIGHLY SELECTIVE; in the case of glycolysis production, the glucose transporter receptors only bind to D-glucose and cannot bind to the mirror image, L-glucose.

Describe how the glucose-Na+ symport is an active-coupled transporter.

The glucose-Na+ symport is an active-coupled transport protein that requires the coupling of Na+ and a glucose molecule before the protein can change conformation and transport the molecules (together) into the cytoplasm.

What determines the direction of passive transport for uncharged and charged molecules? What is electrochemical gradient?

-For UNCHARGED molecules, the direction of passive transport is determined SOLEY by its CONCENTRATION GRADIENT. -For CHARGED molecules, the direction of passive transport depends on the solute's ELECTROCHEMICAL GRADIENT (membrane potential + concentration gradient) *The membrane potential exerts a force on any charged molecule, typically, the negatively charged cytosolic environment will pull in positively charged solutes into the cell, while pushing out negatively charged particles. Additionally, a charged solute will also tend to move down its concentration gradient. The ELECTROCHEMICAL GRADIENT is the NET DRIVING FORCE (composition of membrane potential + concentration gradient) driving the charged solute across a cell membrane. *The electrochemical gradient of a solute determines its net movement; if it is small, not very many particles will move; if it is large, many particles will move.

What is the difference between transporters and channels? What do ion channels permit to pass the membrane?

-TRANSPORTERS: shift small organic molecules or inorganic ions from one side of the membrane to the other by CHANGING SHAPE. -CHANNELS: form tiny HYDROPHILIC PORES across the membrane through which such substances can pass by DIFFUSION. *Ion channels ONLY permit passage of INORGANIC IONS; because these ions are electrically charged, their movements can create a powerful electric force-or voltage- across the membrane. *Channels/ Transporters are usually GATED; opening/closing in response to some stimuli.

What are the 3 main types of ACTIVE TRANSPORTERS? Briefly describe each.

1) COUPLED TRANSPORTERS -couple the UPHILL TRANSPORT of one solute across the membrane to the DOWNHILL TRANSPORT of another (symport and antiport). 2) ATP-DRIVEN PUMPS -couple the UPHILL TRANSPORT of one solute with the HYDROLYSIS of ATP. 3) LIGHT-DRIVEN PUMPS -couple the UPHILL TRANSPORT of one solute to the ENERGY of PHOTONS.

Name 2 types of synapses.

1) ELECTRICAL: direct connection via GAP JUNCTIONS 2) CHEMICAL: TRANSMISSION VIA NEUROTRANSMITTER

Name 5 of the most important INORGANIC ions vital to cell functionality. Which of these is the most plentiful OUTSIDE the cell? Which is the most abundant INSIDE the cell? Why is it important for these charges to remain balanced outside and inside the cell?

1) Na+ *plentiful OUTSIDE the cell. 2) K+ *most abundant INSIDE the cell. 3) Ca^2+ 4) Cl- 5) H+ (protons) *For a cell to avoid being torn apart by electrical forces, the quantity of positive CHARGE INSIDE the cell must be BALANCED by an almost exactly EQUAL QUANTITY of negative charge, and the same is true for the charge in the surrounding fluid. Thus, the high concentration of Na+ OUTSIDE of the cell is electrically BALANCED chiefly by EXTRACELLULAR Cl-, whereas the high concentration of K+ INSIDE is BALANCED by a variety of NEGATIVELY CHARGED organic and inorganic ions (anions) including NUCLEIC ACIDS, PROTEINS, and may cell METABOLITES.

Of the 4 categories of molecules passing the membrane, list the categories from MOST permeable to LEAST permeable across the lipid bilayer. Give examples for each category and briefly explain why the last group is least permeable to the membrane.

1) Small NONPOLAR molecules; O2, CO2, N2, steroids, hormones. (MOST PERMEABLE) 2) Small UNCHARGED POLAR molecules; H2O, ethanol, glycerol. 3) Larger UNCHARGED POLAR molecules; amino acids, glucose, nucleosides. 4) IONS; H+, Na+, K+, Ca2+, Cl-, Mg2+, HCO3-. (LEAST PERMEABLE). *Ions are least permeable to the lipid bilayer because their charge and strong electrical attraction to water molecules inhibit their entry into the inner, hydrocarbon phase of the bilayer.

What are the 3 main types of COUPLED TRANSPORT?

1) Uniport (only transports one molecule) 2) Symport (molecules going SAME direction) 3) Antiport (molecules going in DIFFERENT directions)

Name 4 types of GATED channel/transporter proteins and how they are controlled.

A) VOLTAGE-gated (controlled by membrane potential) B) EXTRACELLULAR LIGAND-gated (controlled by binding of a molecule) C) INTRACELLULAR LIGAND-gated (controlled by binding of a molecule) D) MECHANICALLY-gated (controlled by a mechanical force applied to the channel) *Ion channels are SELECTIVE and GATED.

What is an aquaporin and what molecule is it specific to? What is osmosis?

AQUAPORINS are specialized CHANNEL PROTEINS that greatly facilitate the flow of small, uncharged, WATER molecules to diffuse through the lipid bilayer; they are the fastest known channels. *Osmosis is the movement of WATER DOWN its CONCENTRATION GRADIENT-from an area of LOW solute concentration (HIGH WATER CONCENTRATION) to an area of HIGH solute concentration (LOW WATER CONCENTRATION). *OSMOLARITY (# solute molecules in a solution) has an INVERSE relationship with OSMOSIS (or water activity). *Osmotic swelling pressure = TURGOR PRESSURE

What are neurons? How do they perform their signaling?

Cells involved in receiving, conducting, and transmitting signals from the sense organs to the CNS (brain and spinal cord). *Despite the different classes of neurons, the form of signal is always the SAME, consisting in CHANGES in the ELECTROCHEMICAL MEMBRANE across the NEURON'S PLASMA MEMBRANE. -Neurons (nerve cells) make the most sophisticated use of channels/transporters.

What are delayed K+ rectifier channels and how do they differ from other K+ channels? What 3 conformational states do they adopt? What 2 factors influence the type of conformational change?

Delayed K+ rectifier channels are a type of potassium channel. However, instead of following the concentration and flowing out of the cell, rectifier channels PULL K+ INTO the CELL. *Conformation states: 1) Closed 2) Open 3) Inactivated *The state that the channel adopts depends on -the MEMBRANE POTENTIAL -the TIME that the CHANNEL has SPENT in the OPEN STATE.

Why do failed initiations of an action potential occur on dendrites and neuronal bodies? How would PSP trigger an action potential?

Dendrites/neuronal body membranes have a LOW DENSITY of voltage-gated Na+ channels. An individual post-synaptic potential is normally too SMALL to trigger an action potential. *If the combined magnitude of the post-synaptic potential (PSP) is higher than the threshold, the nerve will fire an action potential.

Why is facilitated diffusion faster than simple?

FACILITATED diffusion is accelerated by specialized MEMBRANE TRANSPORT PROTEINS, allowing it to transport molecules FASTER across than membrane than simple diffusion.

What equation is useful in measuring quantitative assessment of permeability? What units are used? What does positive and negative flux imply?

Flux 1-->2 = RATE of movement of particles per unit area. Flux 1-->2 = - P (C2 - C1) where P= permeability and C= concentration. *Units: Number / Time / Area ex. Molecules / sec / cm^2 -Positive flux implies that movement is along the direction in which flux is determined. -Negative flux implies that movement is OPPOSITE to the direction in which flux is determined.

What is patch-clamp recording and why is the MOST WIDELY used technique for studying ion channels?

In patch-clamp recording, a fine FLASS tube is used as a MICROELCTRODE to isolate and make ELECTRICAL contact with a SMALL AREA of the MEMBRANE at the SURFACE of the CELL. This technique makes it possible to RECORD the ACTIVITY of ION CHANNELS (via oscilloscope screen) in ALL SORTS OF CELL TYPES. *In solution, the current is carried by IONS. *Channels observed in open (peaks) and closed (lines) stages via oscilloscope screen reading.

Chemical Neurotransmitter

Inactive state: Ca^2+ channel closed Active state: Ca^2+ channel open, Ca^2+ flowing in the cell-creating an action potential; the synaptic vesicle carrying the neurotransmitters fuses with the plasma membrane and releases neurotransmitters into the synaptic cleft; later pairing with post-synaptic receptors on a neighboring cell, creating a change in membrane potential and activating another nerve impulse.

What are K+ leak channels? How do they contribute to the membrane potential = 0? What does this mean? What happens when the ion channels open? What other pump contributes to the resting membrane potential and helps with keeping the inside of the cell more negative than the outside?

Ion channels permeable to K+ that RANDOMLY FLICKERS between an OPEN and CLOSED state; largely RESPONSIBLE for the RESTING MEMBRANE POTENTIAL in animal cells. *When the K+ leak channels are CLOSED, the membrane potential is equal to zero because the charges of the membrane (on each side) are EXACTLY equal. Thus, the concentration gradient and membrane potential have reached an equilibrium state in which there is NO NET MOVEMENT of K+ ions. However, when ion channels open, K+ flows down its concentration gradient (out of the cell), creating a membrane potential, that, ultimately drives K+ back into the cell. *The Na+ pump also contributes to the resting potential, expelling 3 Na+ and uptaking 2 K+, keeping the inside of the cell MORE negative than the outside.

What do K+ channels permit to pass through their pores? Do they prefer K+ over Na+? How many different K+ channels does human DNA encode for?

K+ CHANNELS permit K+ to pass through their pores, moreso specific to K+ than Na+. *Human DNA encodes for 100 different types of K+ channels.

When the local change in membrane potential generates a spreading signal across the membrane, how do neurons counteract the signal weakening over increasing distances? What is the traveling wave called? How far can an action potential carry an (unattenuated) signal across a neuron? What other channels/pumps primarily affect the action potential?

Large neurons circumvent this attenuation problem by employing an ACTIVE SIGNALING MECHANISM, where the signal is AMPLIFIED along the way. This traveling wave of electrical excitation is called an ACTION POTENTIAL or NERVE IMPULSE. *The action potential (nerve impulse) can carry a signal (unattenuated) from one end of the neuron to another at speeds of 100 m/sec. *The action potential is due primarily to the interplay between the Na+ channels, K+ channels, and the Na+/K+ pump.

Explain how the Ca^2+ pump is ATP-driven.

Muscle contractions occur via ATP-driven Ca^2+ pumps. Like Na+, Ca^2+ is kept at a low concentration in the cytosol (but less concentrated than Na+in extracellular space) until the influx of Ca^2+ occurs via Ca^2+ channels. *When a muscle cell is stimulated, Ca^2+ floods into the cytosol from the SARCOPLASMIC RETICULUM (SR) and triggers a muscle contraction. After contraction, the Ca^2+ pump uses ATP to PHOSPHORYLATE itself; furthermore, the conformation change eliminates Ca^2+ binding sites and ejects the 2 Ca^2+ ions back into the SR (found in ER) -The influx of Ca^2+ is used for intracellular signaling to trigger processes like muscle contraction, fertilization, and nerve cell communication.

Do neurons just receive signals from their neighboring cells?

No, a single neuron can receive (excitatory and inhibitory) neurotransmitter signals from hundreds of other neurons. *The neuron must COMBINE the information from all synapses and react by either; -FIRING an ACTION POTENTIAL or -REMAINING QUIET

Can the action potential stop abruptly and reverse direction?

No, the action potential can ONLY TRAVEL FORWARD from the site of depolarization. This is because the Na+ CHANNEL INACTIVATION in the aftermath of an action potential PREVENTS the ADVANCING FRONT of DEPOLARIZATION from SPREADING BACKWARD.

Briefly generalize how an action potential generates the secretion of neurotransmitters into the synaptic cleft.

Once an action potential reaches the nerve terminal, it triggers the opening of Ca^2+ channels by depolarizing the presynaptic nerve terminal. Since the Ca^2+ is more concentrated outside the cell, Ca^2+ ions will flow into the cell. The resulting INCREASE in Ca^2+ concentration in the cytosol of the terminal immediately triggers the vesicles (containing neurotransmitters) to fuse with the membrane. Upon fusion, the neurotransmitters are released into the synaptic cleft.

What is the difference between PASSIVE and ACTIVE transport?

PASSIVE transport is the SPONTANEOUS movement of a solute DOWN its concentration gradient via ALL channels and (some) transporter proteins; FACILITATED; moves faster than anticipated by FICK'S LAW; RATE of transport saturates with INCREASE of concentration gradient (log relationship) ACTIVE transport is the STIMULATED movement of a solute across a membrane AGAINST its ELECTROCHEMICAL GRADIENT via a special type of TRANSPORTER protein called a PUMP. *Active transport REQUIRES an INPUT of ENERGY; ATP hydrolysis, a transmembrane ion gradient, or sunlight. NOTE: In passive transport, the solute is moving in both directions (in and out of the cell); however, MORE solute will MOVE IN than OUT until the two concentrations equilibrate.

What is the most important FUNCTION of the Na+-K+ pump?

REGULATION of CELL VOLUME! *A typical animal cell devotes about 1/3 of its energy in FUELING the Na+-K+ pump.

What is the type of glial cell that makes up mylin?

SCHWANN CELLS (types of glial cells) use their plasma membranes to form layers and wrap around axons in a spiral-like fashion.

What factors of a molecule determine its permeability speed?

SIZE and SOLUBILITY *In general, molecules that are smaller and hydrophobic (nonpolar), will diffuse across the membrane quicker.

What occurs when the rising phase reaches its peak, that is, when V membrane > V Na+? Explain.

Self-amplification (the influx of Na+ ions via systematic opening of voltage-gated Na+ channels) continues until the resting membrane state shifts from -60mV to +40mV; i.e. the internal environment of the cell is no longer negatively charged. When V membrane > V Na+, the voltage-gated Na+ channels undergo INACTIVATION. *The inactivation phase (or peak) is marked by the the equal and opposite effects of the membrane potential and concentration gradient of Na+. Once the voltage-gated Na+ channels adopt the inactive conformation, the channel is closed the the Na+ channels remain in this inactivated state until the membrane potential has returned to its initial negative value (resting potential).

Explain how the H+ pump is ATP-driven and used to regulate pH in animal cells. What organelles is the H+ pump found for both plant and animal cells. Do plant cells have Na+ pumps?

Since plant cells, bacteria, and fungi do NOT have Na+ pumps in their plasma membrane, they rely heavily on H+ pumps to import solutes into the cell via the central vacuole; powered by ATP hydrolysis. Additionally, plants set up an electrochemical PROTON gradient across the membrane and create an acid pH in the medium surrounding the cell, operating much like the Na+ pump. *In animal cells, the ATP-dependent H+ pump is found in the lysosomes. The H+ pump is used to ACTIVELY TRANSPORT H+ out of the cytosol and INTO THE ORGANELLE, keeping the cytosol neutral and interior of the organelle ACIDIC; powered by ATP hydrolysis.

Why can't the action potential travel across the myelinated sheaths? How does the action potential travel along the axon? What facilitates the conduction between nodes? Myelination increases the RATE of conduction but how does it conserve energy?

Since the myelinated regions have almost no voltage-gated channels, the NODES OF RANVIER (short, non-myelinated regions inbetween myelinated regions) help the action potential to JUMP along the axon. The nodes of Ranvier contain most of the voltage-gated channels, and the action potential jumps between nodes. *The conduction in the region between the nodes of Ranvier occurs due to PASSIVE INTRACELLULAR DIFFUSION (facilitated by myelin; myelin aids the action potential via conduction down the axon), which is faster than the speed at which action potential travels; also known as SALTATORY CONDUCTION = "to leap". *In addition to increasing the speed of the nerve impulse, the myelin sheath helps in reducing energy expenditure over the axon membrane as a whole, because the amount of sodium and potassium ions that need to be pumped to bring the concentrations back to the resting state decreases, following each action potential.

What is an example of multiple transporters performing one physiological task?

TWO TYPES of GLUCOSE TRANSPORTERS (located at opposite ends, using symport) enable gut epithelial cells to transfer glucose across the epithelial lining of the gut; from the gut lumen, glucose-Na+ symports intake a Na+ coupled with a glucose. Then, the passive glucose uniports (separated by basal and lateral domains of the plasma membranes) release the glucose down its concentration gradient for use by other tissues.

What are inhibitory neurotransmitters? How do they operate in the POST-SYNAPTIC cell? How do they inhibit an action potential from occurring? Give 2 examples.

They open Cl- or K+ channels in the plasma membrane of the POST-SYNAPTIC cell; causes outflow of K+ ions or influx of Cl- ions; this makes it HARDER for the membrane to DEPOLARIZE because of the loss of cations and influx of anions contribute to the continuous negative charge of the internal environment of the cell. Ex. GABA and glycine.

What are excitatory neurotransmitters? How do they operate in the POST-SYNAPTIC cell? What do they create? Give 2 examples.

They open Na+ channels in the plasma membrane of the POST-SYNAPTIC cell; causes an INFLUX of ions into the cell that depolarizes it, and if large enough, can create an action potential. Ex. Acetylcholine (Ach) and glutamate.

What is the ATP-driven Na+ pump? Is it step-dependent?

This pump uses the energy derived from ATP hydrolysis (ATP-->ADP+Pi) to transport Na+ OUT of the CELL as it CARRIES K+ IN; this process is STEP-DEPENDENT, meaning that if any of the steps are prevented from occuring, the process will HALT. *ATP hydrolysis drives conformation changes that induce Na+/K+ exchange, and Pi donated to the pump itself. This process is FAST (10 milliseconds) and CONSERVES ATP (only uses ATP hydrolysis when ions are available for transport). This pump is also known as the Na+-K+ ATPase or the Na+-K+ pump; ouabain (a toxin) can inhibit the pump by preventing the binding of extracellular K+, which will halt the entire cycle.

Name/Explain the main parts of a neuron. -Neuron -Axon -Nerve Terminals -Dendrites

Usually, a neuron has ONE LONG EXTENSION called an AXON, which CONDUCTS SIGNALS AWAY from the cell BODY toward distant TARGET CELLS; the other end of the axon (not directly attached to the neuron) is divided into many branches, which have NERVE TERMINALS that pass the neuron's "messages" to many target cells. The SHORTER branching extensions surrounding the neuron are called DENDRITES, which radiate from the cell body like antennae and provide an ENLARGED SURFACE AREA to RECEIVE SIGNALS from the AXONS of other neurons.

What is a membrane potential?

VOLTAGE DIFFERENCE across a membrane due to a (slight) EXCESS of positive ions on one side and negative ions on the other. *When charges are EXACTLY balanced on each side of the membrane, the MEMBRANE POTENTIAL = 0.

Describe the falling phase of an action potential. What other channels are opening and what ions are flowing out? When do these channels get inactivated? What occurs at the undershoot, when the membrane is hyperpolarized?

Voltage-gated K+ channels open in response to SUFFICIENT DEPOLARIZATION of the membrane, but not nearly as quickly as voltage-gated Na+ channels do. As the local depolarization reaches its peak, K+ ions (carrying positive charge) therefore start to flow out of the cell through these newly opened K+ channels down their electrochemical gradient, temporarily unhindered by the negative membrane potential that normally restrains them in the resting cell. *When the membrane potential returns close to its original resting state, K+ channels get inactivated. By the time all the voltage-gated K+ channels get inactivated, the membrane gets hyperpolarized (undershoot occurs and membrane potential more negative) due to the massive efflux of K+ ions from the cell. *The Na+/K+ pump helps the membrane throughout the action potential, and also becomes inactive upon the membrane returning to its resting potential.

What do voltage-gated Na+ channels permit to pass through their pores? Are they specific to Na+/K+? What do they open and close in response to? Do they adopt conformational changes, similar to that of the delayed rectifier K+ channels?

Voltage-gated Na+ channels permit Na+ ions to pass through their pores. Most Na+ channels show very high specificity to Na+/K+ ions. The voltage-gated Na+ channels open and close in response to the membrane potential. *Voltage-gated Na+ channels also adopt at least 3 different conformation channels; open, closed, and inactivated states.

Give 2 examples of how AMPs make cell membranes permeable.

When AMPs are introduced in solution, the following 2 things may occur: 1) MICELLE FORMATION 2) TOROIDAL PORE FORMATION

What is resting potential? Does it mean that the voltage difference is equal to zero? What is the resting membrane potential range for animal cells? Why is the value expressed as a negative value?

When a cell is "UNSTIMULATED", the EXCHANGE of ANIONS and CATIONS ACROSS the MEMBRANE will be precisely BALANCED; this state, when the VOLTAGE DIFFERENCE across the cell membrane HOLDS STEADY, is called the RESTING POTENTIAL. *This does NOT mean that the voltage difference is equal to ZERO. Rather, the resting membrane potential can be anywhere between -20 and -120 (mV), depending on the organism and cell type. The value is expressed as a NEGATIVE number because the INTERIOR of the cell is MORE NEGATIVELY charged than the EXTERIOR.

Explain the rising phase of an action potential. What occurs and what opens?

When a membrane is stimulated, the membrane potential of the plasma membrane shifts to a less negative value (that is, toward zero). The stimulus which produces SUFFICIENT DEPOLARIZATION of the membrane and surpasses the threshold (V membrane > V threshold), causes the VOLTAGE-GATED Na+ channels to open. Na+ ions flood into the cell, down their electrochemical gradient, and further depolarize the cell (making the internal environment even less negative and opening additional voltage-gated Na+ channels to open). *Na+ channel self-amplification increases depolarization of the membrane using positive feedback (Voltage-gated Na+ channels uptake Na+ and activate other voltage-gated Na+ channels).