2.membranePotential

8/4/2019 2.membranePotential

1/7

Membrane PotentialKeith S Elmslie, Tulane University School of Medicine, New Orleans, Louisiana, USA

A thin lipid bilayer membrane with embedded proteins surrounds all cells. The potential

difference across this membrane depends on the ionic concentrations on either side of this

membrane and the permeability of the membrane to those ions.

Introduction

If you were to place a sensitive electrical measuring devicein the extracellular solution (surrounding a cell) you wouldfind no change in voltage as you moved the device (anelectrode) through this solution. If you made smallinjections of current through the electrode you would findthat there was very little resistance to the electrical currentin this solution. This means that the ions in the solution(sodium (Na1 ), potassium (K1 ), calcium (Ca21 ) and

chloride (Cl2

)) are free to move throughout the solution(no impediments). When, on the other hand, this electrodeis placed into a cell, you measure a decrease in voltage of$ 60mV.Thus,the insideof a cellis 2 60 mVcompared tothe outside of the cell. If you now made small currentinjections, you would find a high resistance. The cellsmembrane resists the movement of ions, which is one factorresulting in the potential difference across the cellmembrane. However, the membrane is not completelyimpermeable to ions. (If that were the case, the potentialdifference across the membrane would be zero.) A class ofproteins called ion channels form passages through themembrane. A small number of ions diffuse across the

membrane generating the membrane potential that can bemeasured by the electrode. Ion channels can be selective forparticular ions and they can be regulated.Thus, thecellcancontrol the passage of ions across its membrane bycontrolling the activity of ion channels. The two forcesthat control the movement of ions through the openchannels are concentration and electrical forces. Theconcentration force is generated by a class of proteinscalled ion pumps that use cellular energy (adenosinetriphosphate, ATP) to establish differential ion concentra-tions across the membrane. The electrical force isestablished by the ion selectivity of the membrane,allowing positively charged ions to leave the cell but

trapping negatively charged ions inside the cell. Togetherthese forces drive ions through the open channels, creatingthe membrane potential. (see Cell membranes: intracellular pHand electrochemical potential.) (see Ion channel biochemistry.)

Resting Membrane Potential: ACharacteristic of All Living Cells

The net movement of molecules in a solution depends othe concentration gradient. Molecules move from areas ohigh concentration to areas of low concentration by thprocess of diffusion (Figure 1a). If a pathway is provideacross the cell membrane, the net direction of the movement of a molecule can be predictedby the difference in thconcentration. For example, urea is a compound that camove through the membrane (it is membrane permeant). Iwe place a cell that contains no urea into a solutio

containing 1 mmol L21

urea, urea will diffuse into the ce(down its concentration gradient) until the cellulaconcentration of urea equals 1 mmol L2 1. (For simplicitwe assume the volume of the cell is small relative to that othe bath, so the concentration of urea in the bath does nochange.) At equilibrium (when the concentration equalized) urea still crosses the membrane, but the movement into the cell equals the movement out of the cell; thais, the net movement of urea is zero at equilibrium. Thusconcentrationgradientsform a chemical force directing thnet movement of molecules. All living cells maintaidifferential ion concentrations across the cell membrane sthat the concentration of each ion is larger on one side o

the membrane than the other. Table 1 lists the maiphysiological ions for a typical mammalian neurontogether with their intracellular and extracellular concentrations. While these values are for a neuron, similar ioconcentrations are found for other cells. Note that thconcentration difference is not the same for each ion; foexample, the potassium (K1 ) concentration is higher othe inside of the cell, while the sodium (Na1 ) concentration is higher outside the cell. Since membrane is permeablto K1 and Na1 , the chemical force will drive these ions t

Article Contents

Introductory article

. Introduction

. Resting Membrane Potential: A Characteristic of All

Living Cells

. Action Potentials: A Characteristic of Excitable Cells

. Electrical Signals Produced by Ionic Movement Acros

the Plasma Membrane: The Roles of Channels and

Pumps

. Single-ion Electrochemical Equilibrium: The Nernst

Equation

. Multi-ion Electrochemical Equilibrium: The Goldman

Equation

. High Resting Permeability to Potassium and the

Membrane Potential

. Summary

ENCYCLOPEDIA OF LIFE SCIENCES 2001, John Wiley & Sons, Ltd. www.els.net


2/7

diffuse down their concentration gradients. In order tomaintain the gradients, the cell must expend energy in theform of ATP to pump the ions against their concentrationgradient. (see ATPases: ion-motive.)

The movement of urea and other uncharged moleculescontrolled by the concentration gradient; however, electrical forces together with chemical forces control thmovement of ions. To illustrate the electrical force, let uassume a cell containing 100 mmol L2 1 KCl is placed inta solution of 10 mmol L2 1 KCl, but the membrane is onlpermeant to K1 (Figure 1b). As K1 begins to diffuse from

the cell down its concentration gradient, Cl2

is left behindas it cannot diffuse across the membrane. Thus, as Kleaves the cell a negative potential is established across thmembrane (because of the build-up of negative Cl 2 ioninside the cell). Opposite electrical charges attract, so thnegative potential is a force that pulls the K1 back intthe cell. Note that in the case of K1 the electrical anchemical forces oppose each other in a resting ce(membrane potential (Em) 5 2 60 mV). The chemicaforce drives K1 out of the cell, while the electrical forcedrive K1 into the cell. K1 will leave the cell (making thmembrane more negative) until the electrical forcbecomes large enough to balance the chemical force. Th

potential at which this balance is achieved is called thequilibrium potential. The electrical and chemical forcetogether are termed the electrochemical force or gradien

Differential ion concentration is one of the factorneeded to generate the resting membrane potentia(typically between 2 60 and 2 100 mV); however, npotentialcan develop if the membrane is equally permeablto all ions. The other factor in generating a membranpotential is the selective permeability of the membrane. Arest, the membrane is selectively permeable to K1 . Thuthe resting membrane potential of all cells is sensitive to thK1 gradient. If the extracellular K1 concentration raised without altering the intracellular K1 concentration

the membrane potential is brought closer to zero (depolaized). Scientists studying the effect of membrane potentiaon cellular physiology and/or biochemistry often manipulate the extracellular K1 concentration to alter thmembrane potential. Equations presented below allowcalculation of the membrane potential based on the ioconcentration when only a single ion is permeant. Whe

Time = zero

100mmolL1 K+

(b)

100mmolL1 Cl

100mmolL1 K+

Time = infinity(equilibrium)

100mmolL1 Cl

Time = zero

Zerommol L1 urea

(a)

Time = infinity(equilibrium)

1mmolL1 ureaChemical force

1mmolL1 urea

Chemical force= zero

1mmolL1 urea

Electrical force= zero

10mmol L1 K+

Chemical forceEm = 0mV

10mmol L1 Cl

Em = 58mV

Electrical force10mmol L1 K+

Chemical force

10mmol L1 Cl

Figure 1 The forces that control the movement of molecules across the

cell membrane. (a) Chemical forces control the movement of nonionicmolecules across the membrane. At time zero a cell is placed into a bathcontaining 1 mmol L21 urea. The concentration gradient across the

membrane is initially large, which creates a large chemical force to moveurea into the cell. At equilibrium, the concentration of urea is equal across

the membrane and the chemical force has dropped to zero. The twoheaded arrow indicates that the urea still crosses the membrane, but atequilibrium efflux equals influx. (b) In this example, the cell membrane is

permeableto K1 ,butnotCl2 . At time zero, thecell containing 100mmolL21 KCl is placed into a bath containing 10 mmol L 21 KCl. Initially, theconcentration gradient generatesa concentration forcethat drives K1 out

of the cell. With time (a few milliseconds), a negative potential is createdinsidethe cell bythe Cl2 left behindby K1 efflux. This build-up of negative

charge creates an electrical force that pulls K1 back into the cell. Atequilibrium the negative membrane potential generates an electricalforcethat exactly balancesthe chemicalforce. Thus, thenet K1 flux(summation

of inward and outward flux) equals zero. Note that, unlike urea, theconcentration of K1 is virtually unchanged between the initial conditionsand equilibrium. This is because only a small number of K 1 ions need to

cross the membrane to generate a voltage large enough to balance thechemical force.

Table 1 Concentrations of some ions outside and inside a mammalian neuron

Ion [Outside] (mmol L2 1) [Inside] (mmol L21) Ex (mV)

K1 5 150 2 86

Na1 150 15 +58

Cl2 125 9 2 66

Ca21 2 0.0001 $+250A2 108 N/A

Values obtained from Hille (1992), Ganong (1997) and Matthews (1991). The equilibriumpotentials (Ex) are calculated for room temperature of 208C. These Ex values wouldincrease by a factor of 1.06 for body temperature (378C). A

2 represents membraneimpermeant organic anions (primarily proteins, amino acids and phosphate ions).Because these anions do not cross the membrane, they do not have an equilibriumpotential. N/A, not applicable.

Membrane Potential

2


3/7

the membrane is permeable to multiple ions, a secondequation will be presented that considers both the ionconcentrations and the relative membrane permeability inthe calculation of membrane potential.

Cells use differential ion concentrations (and theresulting membrane potential) for many important func-tions. As we will see below, excitable cells (nerve and

muscle cells) use the membrane potential for electricalsignalling. However, nonexcitable cells (the majority ofcells in the body) use the force generated by theelectrochemical gradient to aid in the transport of essentialsubstances across the cell membrane. In each case, theenergy of the ion gradient of one ion (typically Na1 ) isused to move a second molecule. For example, amino acidsare transported into the cell via the Na1 amino acidcotransporter protein. The concentration of amino acids ishigher inside the cell and so energy must be used to movethem against their concentration gradient. The cotran-sporter binds the amino acid and Na1 simultaneously anduses the energy of the Na1 electrochemical gradient to

power the movement into the cell. Another example of thistype of transport is called the Na1 /Ca21 exchanger,because Na1 and Ca21 are moved in opposite directions.The intracellular concentration of calcium (Ca21 ) ismaintained at a very low level ($ 100 nmolL2 1) by thecells. This is compared to an extracellular concentration of$ 2mmolL2 1. As with Na1 , both the electrical andchemical forces favour the movement of Ca21 into the cell.However, Ca21 is an important cellular messenger andincreases in the intracellular concentration of Ca21 aretherefore used to signal events. For this reason, randomincreases in intracellular Ca21 must be opposed, andsignalling-induced increases must be rectified. One of the

mechanisms the cell uses to maintain low intracellularCa21 concentration is the Na1 /Ca21 exchanger. Thisproteinuses the electrochemicalNa1 gradient to transportCa21 out of the cell. Thus, the electrochemical forcescreated by the ion gradient and selective membranepermeability play very important roles in cell physiology.(see Transport of small molecules.) (see Ion transport acrossnonexcitable membranes.) (see Calcium signalling and regulationof cell function.)

Action Potentials: A Characteristic of

Excitable CellsAll cells have a resting membrane potential, but onlyexcitable cells use the membrane potential to generatesignals. The two types of electrical signals are receptorpotentials and action potentials. Receptor potentials aregenerated in sensory nerve terminals in response to sensorystimulation and in postsynaptic cells in response toactivation of receptor/ion channels by neurotransmitters.These potentials travel (or propagate) passively along the

membrane. Passive propagation means that these potentials decay exponentially with distance from their startinpoint. Action potentials, on the other hand, are activelpropagated along the membrane. This is accomplished baction potentials being sequentially induced in each smapatch of membrane as they move along. The ionmechanisms involved in the generation and propagatio

of the action potential is described elsewhere. Briefly, thaction potential involves a transient influx of Na1 thadepolarizes the membrane to nearly 1 40 mV. This ifollowed by a K1 efflux that rapidly returns the membranto its resting level. The propagation occurs because thNa1 influx at one membrane patch leads to thdepolarization and the subsequent Na1 influx in the nexpatch. (see Action potential: generation and propagation.)

The action potential is the mechanism by whicinformation is transmitted within most neurons in thnervous system (some neurons in the retina and ear usonly receptor potentials). The important property of thaction potential is that it can be transmitted long distance

without alteration. This is extremely important because thaxon extending from a single neuron can be over 1 metrlong (e.g. sensory neurons that have axons extending fromthe tip of thetoes to the base of the brain). The informatiocarried by action potentials is accurately transmitted ovethese vast distances. (see Action potential: ionic mechanisms.)

Electrical Signals Produced by IonicMovement Across the Plasma

Membrane: The Roles of Channels andPumps

Under physiological conditions, the membrane bilayer impermeant to ions. The lipids that comprise the membrane are hydrophobic (dislike water), while ions arhydrophilic (like water). Thus, the ions will remain in thwater and avoid the hydrophobic membrane. The ioncross the membrane via a class of transmembrane proteincalled ion channels (Figure 2). These proteins form waterfilled pores through the membrane that provide thpathway for ions to move in response to the electrochemical forces. One class of ion channels passes cation

(positively charged ions) and the other class passes anion(namely Cl2 ). Within the cation class there exist iochannels that are nonspecific, in that they pass cationwithout strongly selecting betweenthem. More commonlyion channels are selective in that they will primarily pass single ion, such as Na1 , K1 or Ca21 . These ion channeare named according to their primary permeant ion (i.eNa1 channels, K1 channels and Ca21 channels). (seeLipbilayers.) (see Ion channels.) (see Sodium, calcium and potassiumchannels.)

Membrane Potential


4/7

The role of the ion channels is to set the permeability ofthe membrane. The majority of those that are involved insetting the resting membrane potential are permeable toK1 . A smaller number are permeable to Na1 . These ionchannels are often called leak channels because they arealways slowly leaking K1 and Na1 ions to maintain astable resting membrane potential. However, the activity

of these channels would result in the loss of the ionicgradients across the cell membrane if it were not for the ionpumps, a class of proteins that use energy to move ionsacross the membrane. One type of pump described abovewas the Na1 /Ca21 pump, which used the energy of theNa1 gradient to move Ca21 out of the cell. Unlike theNa1 /Ca21 pump, the ion pump that maintains the Na1

and K1 gradients utilizes the energy derived from ATPhydrolysis to power the movement of ions. This energy is

required because the ions are transported across thmembrane against their concentration gradients. The moimportant of these pumps is the Na1 /K1 ATPase (alscalled the Na1 /K1 pump). This protein simultaneousltransports (or pumps) Na1 out of the cell and K1 intthe cell. The Na1 /K1 ATPase is the reason for thdifferential concentrations of Na1 and K1 across the ce

membrane (Table 1). Thus, the leak channels establish thresting membrane potential by allowing Na1 and K1 tcross the membrane, while the Na1 /K1 ATPase maintains the differential ion concentrations. (see Potassiuchannel diversity: functional consequences.) (see Adenosine triphosphate.)

Single-ion Electrochemical EquilibriumThe Nernst Equation

As stated above, the resting membrane potential primarily controlled by the K1 concentration across thcell membrane. Thus, as a first approximation, we camodel the membrane of a resting cell as being exclusivelpermeable to K1 . This simplification will allow us texplore the relationship between the chemical and electrical forces discussed above. Specifically, for a giveconcentration gradient across the membrane, we cacalculate the membrane potential at which the electricaand chemical forces are balanced. This potential is callethe equilibrium potential. To illustrate this, consider thexample in Figure1b where a cell containing 100 mmol L2

KCl is placed into a solution of 10mmol L2 1 KCl, and thmembrane is selectively permeable only to K1 . At thequlibrium potential the K1 influx driven by electricaforce is equal to K1 efflux driven by the chemical forceThe equilibrium potential can be calculated from the ioconcentrations across the membrane using the Nernequation: (see Nernst, Walther Hermann.)

Ex RT

zF ln

XoXi

1

where Xis the ion in question (K1 in this example), R isthgas constant (8.315 J K2 1 mol2 1), Tis the temperature idegrees Kelvin, z is the valence of ion X (z 5 1 1 for K1

and Fis Faradays constant (9.648 104 Cmol21). Below

is an example calculation using the K

1

concentrationfrom Figure 1 and a room temperature of 208C,

Ex 8:315JK1 mol1 293K

1 9:648 104 Cmol1 ln

10mmolL1o100 mmol L1i

which reduces to EK 5 2 0.0583J C2 1. Since 1J (jou

le) 5 1 V C (volt coulomb), EK 5 2 58.3 mV.In biology we generally work with a simplified form o

the Nernst equation where room temperature is 208C anthe natural log (ln) has been transformed into log10. Th

Extracellularsolution

Plasmamembrane

Cytoplasm

ATP

ADP + Pi

(a)

(b)

Figure 2 Ion channels and pumps move ions across the plasmamembrane. (a) Ion channels form water-filled pores that permit the

hydrophilic ions to pass through the hydrophobic lipid bilayer membrane.The direction of ion flux through the open channel is governed byelectrochemicalforces. (b)Ion pumps move ions byusingenergy from ATP

hydrolysis. In this cartoon the pump will simultaneously transport twodifferent ions in opposite directions (analogous to the Na1/K1 ATPase).

The pumps move the ions against their concentration gradients. In other

words, the ions are moved from an area of low concentration to an area ofhigh concentration. From left to right: ions bind to sites in the pump (left).

This binding triggers the hydrolysis of ATP (middle), which alters theconformation of the pump to release the ions on the opposite side of themembrane (right). Once the ions are released the pump returns to itsresting position, ready to bind and transport more ions.

Membrane Potential

4


5/7

form of the equation is:

Ex 58mV

z log

XoXi

2

It may be surprising that we are using initial conditions to

calculate an equilibrium voltage. Indeed,it is clear thationsmust cross the membrane to create a voltage. If ions arecrossing the membrane, how can we use initial concentra-tions in this calculation? To answer this question, we needto know how many ions need to cross the membrane toachieve the equilibrium potential. Based on the electricalproperties of the cell membrane, it can be calculated thatonly approximately one billionth of the total number ofK1 ions need to cross the membrane in order to achievethe equilibrium potential. Since the net movement of only asmall number of ions is required to counter a largeconcentration force, it is valid to use the initial concentra-tions to calculate the equilibrium potential.

The K1

concentrations illustrated in Figure 1 were usedto simplify the calculation of the equilibrium potential. Ascan be seen in Table 1, the K1 concentration inside the cellis higher than in our example, and the concentrationoutside is lower. This results in the K1 equilibriumpotential of a real neuron being hyperpolarized to that wecalculated in our example ( 2 86 mV versus 2 58 mV). Inaddition to K1 , an equilibrium potential can be calculatedfor each permeant ion (Table 1). Note that Na1 ions aremore concentrated in the extracellular solution comparedto the cytoplasm, which results in a positive equilibriumpotential. Thus, unlike K1 , at resting membrane potentialboth the chemical force and the electrical force are directed

inward for Na1

.Because the equilibrium potential is the voltage at which

ion influx and efflux are balanced, when the membranepotential deviates from the equilibrium potentialthose ions move in a direction that will return themembrane potential to the equilibrium potential. Forexample, if the membrane potential is set to 2 40 mV, K1

will flow out of the cell in order to hyperpolarize themembrane to EK ( 2 58 mV in the example ofFigure 1). Onthe other hand, if the membrane potential is 2 80mV, K1

will flow into the cell to depolarize the membraneto EK. Thus, with a constant concentration gradient theion flux is directly proportional to the difference between

the membrane potential (Em) and the equilibrium potentialfor that ion (Ex). This difference is called driving forceand is formally written Em 2 Ex. Driving force dictates thedirection of ion flux, while the magnitude of ion flux isdetermined by the driving force and the membranepermeability to that ion. One way to describe membranepermeability is as the conductance of the membrane toan ion (Gx), which is the ease with which an ion willcross the membrane. Ion flux can be measured as ioniccurrent (I, in coulombs per second, C s2 1). Ohms law

(E5 IR) can be used to relate current with driving forcand conductance:

Ix 5 Gx (Em 2 Ex) [3

where Gx 5 1/Rx (resistance) and E 5 driving forc(Em 2 Ex).

Multi-ion Electrochemical Equilibrium:The Goldman Equation

The single ion example nicely illustrates the forces on iomovement, but real cells have multiple permeant ionUsing the Nernst equation, we can calculate the equilibrium potential for each ion, but with multiple permeanions the membrane potential is no longer equal to thequilibrium potential of a single ion. In order to calculatthe membrane potential, we need to know the relativ

membrane permeability of each ion. This can be illustrateusing Figure 3a, which shows theion gradients forNa1 anK1 for a typical mammalian cell. The equilibriumpotentials under these conditions are 2 86mV and1 58mV for K1 and Na1 , respectively. Thus, in thextreme situation, if the membrane were exclusivelpermeant to K1 the membrane potential would be2 86 mV. Alternatively, if the membrane were exclusivelpermeant to Na1 , the membrane potential would be1 58 mV. Of course, this never happens. In reality the cemembrane is simultaneously permeant to several ionThus, the membrane potential is related to the relativpermeability of the membrane to the permeant ions. Fo

example, if the membrane were equally permeable to Naand K1 the membrane potential would be the average oENa and EK, which is 2 14 mV. In a multi-ion system, wneed to know the equilibrium potential for each permeanion and the membrane permeability for each ion before wcan calculate the membrane potential (Em). This relationship can be quantified using the Goldman equation, whicis also called the constant field equation:

Em RT

F ln

pKKo pNaNa

o pClCli

pKKi pNaNa

i pClClo

4

where pX is the permeability of ion X and R, Tand Fhavthe same meaning as in the Nernst equation. Note that th

intracellular and extracellular Cl2 concentrations arreversed from those of Na1 and K1 . This is done to keethe sign positive, since ln (A/B) 5 2 ln (B/A). In thGoldman equation,each concentrationterm is scaled by ipermeability. This demonstrates that an ion cannocontribute to the membrane potential if its membranpermeability is zero.

It is much easier to experimentally measure relativpermeability than actual permeability. In such a casepermeability is usually expressed in reference to th

Membrane Potential


6/7

potassium permeability. Therefore, the Goldman equationtypically takes the form of:

Em RT

F

lnKo bNa

o cCli

K

i bNa

i cCl

o5

where b 5pNa/pK and c 5pCl/pK. The equation can befurther simplified by removing Cl2 . This simplification isvalid in neurons because the Cl2 conductance is smallrelative to that of potassiumand contributes little to restingmembrane potential. However, such simplification is notappropriate for other cells, like skeletal muscle cells, whereresting Cl2 conductance is high. This simplified form ofthe Goldman equation is:

Em RT

F lnK

o bNa

oKi bNa

i6

where b has the same meaning as in eqn [5]. Note that theequation can be further simplified by converting thenatural log (ln) into the log10 and using room temperatureto convert RT/Fto 58 mV. If one is to use this form of theGoldman equation (eqn [6]) in research, it is up to theinvestigator to verify thatpCl/pK ratio is negligible and thatCl2 contributes little to membrane potential.

High Resting Permeability to Potassiumand the Membrane Potential

The simplified form of the Goldman equation allows us texplore the relative permeabilities of Na1 and K1 i

relationship to the membrane potential. Using the ioconcentrations of Table 1, we can calculate a Em of2 62 mV if the membrane were 20 times more permeable tK1 than Na1 (b 5 0.05). This value is close to that for neuron at rest.Therefore, we conclude that a neuron at resis $ 20 times more permeable to K1 than to Na1 . On thother hand, if the membrane were 20 times more permeablto Na1 than K1 (b 5 20), Em would equal 1 48 mVwhich is close to thepeak of the action potential. From thwe can conclude that at the peak of the action potential thNa1 conductance is $ 20 times larger than that of K1

This change in the relative permeability of the membranto Na1 occurs as a result of the activation of voltag

dependent Na1

channels. The activation of these channeis transient, but the resulting depolarization activatevoltage-dependent K1 channels, which help retur(repolarize) the membrane to the resting potentia(see Sodium channels.) (see Voltage-gated potassium channels.)

In the example in Figure 1, Cl2 was membranimpermeant. Recall that this was the source of the negativcharge remaining in the cell which resulted in the electricaforce that pulled K1 back into the cell. However, thGoldman equation has a Cl2 permeability term. I

K+ 5mmol L1

5mmol L1 K+

150mmol L1 Na+

125mmol L1 Cl

Em = EK = 86mV

(a)

9mmol L1 Cl

150mmol L1 K+

9mmol L1 Cl

5mmol L1 K+

150mmol L1 Na+

125mmol L1 Cl

Em = ENa = +58mV

(b)

150mmol L1 K+

15mmol L1 Na+

9mmol L1 Cl

Na+ 150mmol L1

Cl125mmol L1

108 mmol L1 A

15mmol L1 Na+150mmol L1 K+

15mmol L1 Na+

Em = ? mV

Na+K+ pump

Figure3 Relativepermeability of ions determines themembranepotential fora given setof ionconcentrations. (a)Two examples where eitherK 1 (lef

or Na1 (right) is the only permeant ion. In each case, the membrane potential equals the equilibrium potential for the permeant ion. (b) In a real cell thmembrane is permeable to K1 , Na1 and Cl2 . The Goldman equation is required to determine the membrane potential, as it considers both the ionconcentrations across the membrane and the permeability of each ion.

Membrane Potential

6


7/7

addition, it was stated above that Cl2 permeability is quitehigh in some cells (e.g. skeletal muscle cells). Yet these cellsmaintain an electrochemical force as strong as the cells withlittle Cl2 permeability. How can the negative internalpotential develop if the membrane is permeable to Cl2 ? Inreal cells, a diverse group of organic molecules that cannotreadilycross the membrane function as impermeant anions

(Table1, Figure3).Thisgroupofanions,referredtoasA2

inTable 1, includes proteins, charged amino acids (glutamateand aspartate) and phosphate ions.

In a cell with multiple permeant ions the membranepotential does not equal the equilibrium potential for anyion. Therefore, ions will move across the membrane in aneffort to drive the membrane potential to their respectiveequilibrium potentials. Without intervention the ionicgradients would decline with time, resulting in a loss ofmembrane potential. As discussed above, ion pumpsprevent the loss of the ionic gradient. The Na1 /K1

ATPase maintains the Na1 and K1 gradient, but it alsocontributes to the membrane potential. This contribution

comes from this protein moving 3 Na1

out of the cell forevery2K1 it transports into the cell. This 3 : 2 ratio meansthat the pump generates a negative current as it works andthis current has been shown to hyperpolarize the cellmembrane. In one study, the Na1 /K1 pump was shownto contribute $ 10 mV to the resting membrane potential.In the absence of the pump (blocked using a drug calledoubain), the resting membrane potential averaged$ 2 65 mV. However, the resting potential was 2 75mVwith the pump working.

Summary

The regulation of selective ion channels allows the cell tset the permeability of its membrane to inorganic ions. Thpermeability of the membrane is one factor involved isetting the membrane potential. A second factor is thgradient of ion concentrations across the membrane. Thi

gradient is established by ion pumps that use the energy oATP hydrolysis to move ions from areas of low concentration to areas of high concentration. For each permeant iowe can calculate the membrane potential at which thchemical and electrical forces are balanced so that the neflux of that ion is zero. Intracellular impermeant anionstogether with the concentration gradient and relativelhigh K1 permeability, establish a resting membranpotential where the inside of the cell is $ 60 mV negativto the outside. Excitable cells (e.g. neurons) have voltagedependent ionchannels that are selective for Na1 andK1

Activation of the Na1 channels depolarizes the membrantowards the Na1 equilibrium potential. Subsequen

activation of voltage-dependent K1

channels returns thmembrane to its resting potential.

Further Reading

Ganong WF (1997) Review of Medical Physiology, 18th edn. Stamfor

CN: Appleton and Lange.

Hille B (1992) Ionic Channels of Excitable Membranes, 2nd ed

Sunderland, MA: Sinauer.

Levitan IB and Kaczmarek LK (1997) The Neuron: Cell and Molecula

Biology, 2nd edn. New York: Oxford University Press.

Matthews GG (1991) Cellular Physiology of Nerve and Muscle, 2nd ed

Boston, MA: Blackwell Scientific.

Membrane Potential

2.membranePotential

Documents

Transcript of 2.membranePotential