Membrane Potential

Membrane potential

Separation of charges across the membrane

Or

Difference in relative number of cations and anions in the ECF

Separated charges create the ability to do work

Membrane potential is measured in millivolts

1mv = 1/1000 volts

Chapter 3 The Plasma Membrane and Membrane PotentialHuman Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

Which has the greatest membrane potential?

Plasma membrane of all living cells has a membrane potential (polarized electrically)

Due to differences in concentration and permeability of key ions ie Na+ K+ and large intracellular proteins b/w ECF & ICF

Nerve and muscle cellsExcitable cellsHave ability to produce rapid,

transient changes in their membrane potential when excited which serves as electric signals

Resting membrane potential (RMP)

Constant membrane potential present in cells of non excitable tissues and those of excitable tissues when they are at

rest

Generation and maintenance of RMPThe unequal distribution of a few key ions b/w

the ICF and ECF and their selective movement through the plasma membrane are responsible for the electrical properties of the membrane

In body electric charges are carried by ions .

So the ions primarily responsible for the generation of resting membrane potential are Na+ , K+, and A-

Resting Membrane Potential

The Resting Potential

inside

outside

Resting potential of neuron = -70mV

+

-

+

-

+

-

+

-

+

-

Table 3-3, p. 75

The concentration difference of Na+ and K+ are maintained by the Na+ K+ pump.

Since the plasma membrane is impermeable to proteins so A- are inside the membrane

More permeability of K+ as compared to Na+ in resting stateThe plasma membrane is more permeable to K+ in resting state than Na+ because the membrane has got more leak channels for K+ than for Na+

Moreover the hydrated form of K+ is smaller than the hydrated form of Na+

Key point

Concentration gradient for K is towards outside and for Na is towards inside but the electric gradient for both of these ions is towards the negatively charged side of the membrane

Normal value of RMP in different cells

Resting membrane potentials for cells generally range: -20 mV to -200mV

 TYPE OF CELL RMP

SKELETAL MUSCLE - 90 mvs

SMOOTH MUSCLE - 60mvs

CARDIAC MUSCLE - 85 to - 90 mvs

NERVE CELL - 70 mvs

Effect of sodium-potassium pump on membrane potential

Makes only a small direct contribution to membrane potential through its unequal transport of positive ions

Only 20% of the MP is directly generated by Na K pump

80% of the MP is caused by the passive diffusion of Na and K down the concentration gradient

Effect of movement of K+ alone on MP (K+ equilibrium potential)

Plasma membrane

ECF ICF

Concentrationgradient for K+

Electricalgradient for K+

EK+ = –94mV

•.•MEMBRANE POTENTIAL CAUSED BY DIFUSION OF K IONS= -94 MV (K+ equilibrium potential)

•Nernst equation:•Used to calculate the equilibrium potential caused by single ion

•EMF= ± 61 Log conc. outside ____________ Conc inside

•. Therefore : for K+ ion•EMF= ± 61 log conc. Of K+ Outside

____________

conc. Of K+ inside

EMF = ± 61 log 4 ____

140

= 61 log 1

____

35

= - 61 × (-1.54) because log of 1/35 is -1.54

= - 94 mvs

Effect of movement of Na+ alone on MP (Na+

equilibrium potential)

Plasma membrane

ECF ICF

Concentrationgradient for Na+

Electricalgradient for Na+

ENa+ = +61 mV

•Similarly for Na ions •EMF = ± 61 log conc. Outside

______________

conc. Inside

= +61 log 150/15

= +61 × 1 (log of 10=1)

= +61 mvs

Goldman equation:

Used to calculate the equilibrium potential of 2 or more ions

Therefore combining the equilibrium potential of K (-94) & Na (+61)

= - 86 mVs

The membrane is so impermeable to Chloride that you drop it from the equation

Maintaining the Resting Potential by Na+ K+ pumpNa+ ions are actively transported (this

uses energy) to maintain the resting potential.

The sodium-potassium pump (a membrane protein) exchanges three Na+ ions for two K+

ions. since more +ve ions move outside so causes negativity of -4 mvs on inside

inside

outside

Na+

Na+

K+K+

Na+

NET RMP

Net RMP = - 86 - 4 = -90mvsThis means when the cell is at rest it has negativity of

-90 mvs inside i.e. inside the cell there is 90 mvs more negative as compared to outside the cell

Resting Membrane Potential summaryIonic differences are the consequence of:

•Different membrane permeabilities due to passive ion channels for Na+, K+, and Cl-

•Operation of the sodium-potassium pump

Fig. 3-23, p. 79

Plasma membrane

ECF ICF Relatively large netdiffusion of K+

outward establishesan EK+ of –90 mV

No diffusion of A– across membrane

Relatively small netdiffusion of Na+

inward neutralizessome of thepotential created byK+ alone

Resting membrane potential = –70 mV

(A– = Large intracellular anionic proteins)Fig. 3-22, p. 78

Fig. 3-22, p. 78

Usefulness?Neurons and muscle fibers can alter membrane

potential to send signals and create motion. So called excitable tissues because when they

are excited by appropriate stimulation they can rapidly and transiently alter membrane permeabilities to the involved ions so bringing fluctuations in membrane potential which bring about nerve impulse in nerve cells and triggering contraction in muscle cells

Changes in ion movement in turn are brought about by changes in membrane permeability in response to a triggering agent or a stimuli

•The stimulus:

It is an external force or event which when applied to an excitable tissue produces a characteristic response. Examples of various types of stimuli are:1)Electrical: use to produce an action potential in neurons .2)Hormonal: hormones are released i.e. adrenaline act on heart to increases its rate3)Thermal: stimulation of thermal receptors in skin by hot or cold objects.4)Electromagnetic receptor: stimulation of rods & cone of retina by light. 5)Chemical: stimulation of taste receptors on the tongue6)Sound: stimulation of auditory hair cells

•Sub-threshold stimuli: A stimulus which is too weak to produce a response

•Threshold stimuli:Minimum strength of stimulus that can produce excitation is called threshold stimuli.

Electrical signals are produced by changes in ion movement across the plasma membrane

Triggering agent (stimulus) Change in membrane permeabilityAlter ion flow by opening and closing of gates

Membrane potential fluctuatesElectrical signal generated

Types of electrical signals

Two types of signals are produced by a change in membrane potential:

graded potentials (short-distance signals)

action potentials (long-distance signals)

Terminology Associated with Changes in Membrane Potential

F8-7, F8-8

• Polarization-

•Depolarization- a decrease in the potential difference between the inside and outside of the cell.

•Hyperpolarization- an increase in the potential difference between the inside and outside of the cell.

• Repolarization- returning to the RMP from either direction.

•Overshoot- when the inside of the cell becomes +ve due to the reversal of the membrane potential polarity.

Terminologies

PolarizationDepolarizationRepolarizationHyperpolarization

Graded PotentialsShort-lived, local changes in membrane potential

(either depolarizations or hyperpolarizations)

Cause passive current flow that decreases in magnitude with distance so serve as short distance signals

Their magnitude varies directly with the strength of the stimulus – the stronger the stimulus the more the voltage changes and the farther the current goes

Sufficiently strong graded potentials can initiate action potentials

Graded PotentialsThe Stronger a triggering event, the larger

the resultant graded potentialGraded Potential spread by passive Current

flow.Graded potentials die over short distances

K+ leaks out of the membraneDecremental: gradually decreases

If strong enough, graded potentials trigger action potentials

The wave of depolarization or hyperpolarization which moves through the cell with a graded potential is known as local current flow.

Current Flow During a Graded Potential

Chapter 4 Principles of Neural and Hormonal CommunicationHuman Physiology by Lauralee Sherwood ©2010 Brooks/Cole, Cengage Learning

Chapter 4 Principles of Neural and Hormonal CommunicationHuman Physiology by Lauralee Sherwood ©2010 Brooks/Cole, Cengage Learning

Graded PotentialOccurs in small, specialized region of

excitable cell membranes Magnitude of graded potential varies directly

with the magnitude of the triggering event

Examples of graded potentials are:

1)Receptor potential.

2)Post synaptic potential

3)Slow wave potential

4)End plate potential

5)Pace maker potential

•A graded potential depolarization is called excitatory postsynaptic potential (EPSP). A graded potential hyperpolarization is called an inhibitory postsynaptic potentials (IPSP).

•They occur in the cell body and dendrites of the neuron.

Changes in Membrane Potential

Graded Potentials

Voltage changes in graded potentials are decremental, the charge is quickly lost through the permeable plasma membrane

short- distance signal

•Graded potentials travel through the neuron until they reach the trigger zone. If they depolarize the membrane above threshold voltage (about -55 mV in mammals), an action potential is triggered and it travels down the axon.

F8-10

Graded Potentials Above Threshold Voltage Trigger Action Potentials

Action Potentials (APs)

The AP is a brief, rapid large change in membrane potential during which potential reverses so that inside of the excitable cell transiently becomes more +ve than the outside.

APs do not decrease in strength with distance so serve as long distance signals.

Events of AP generation and transmission are the same for skeletal muscle cells and neurons

Course of the Action PotentialThe action potential begins with a partial

depolarization [A].When the excitation threshold is reached

there is a sudden large depolarization [B].This is followed rapidly by repolarization [C]

and a brief hyperpolarization [D].

Membrane potential (mV)

[A]

[B] [C]

[D] excitation threshold

Time (msec)-70

+40

0

0 1 2 3

Marked changes in membrane permeability and ion movement lead to an action potential (AP)Passive diffusion of K+ makes greatest

contribution to the RMP due to more permeability of plasma membrane to K+ through leak channels at rest.

During an AP marked changes in membrane permeability to Na+ and K+ take place permitting rapid fluxes down their electrochemical gradient

These ions carry the current responsible for the potential changes that occur during an AP

Action potential takes place as a result of the triggered opening and subsequent closing of 2 specific types of channels

Voltage gated Na+ channelsVoltage gated K+ channels

ROLE OF VOLTAGE GATED Na+ CHANNEL & VOLTAGE GATED K+

CHANNELS IN ACTION POTENTIAL

Voltage gated Na+ channels Most important channels during APIt has two gates:ACTIVATION GATES: At RMP activation gates

are closed so no Na+ influx at RMP thru these channels

These activation gates open when membrane potential become less negative than during resting state then the activation gates of these voltage gated channels open so increasing Na+ permeability to 500- 5000 fold.

Inactivation of Na+ channelsThe same increase in voltage that open the

activation gates also closes the inactivation gates but closing of gates is a slower process than opening so large amount of Na+ influx has occurred

Another important feature of Na+ channels inactivation is that the inactivation gate will not reopen until the membrane potential returns to or near the original RMP.

•.

Voltage gated K+ channelDuring RMP Voltage gated K+ channels are closedThe same stimulus which open voltage gated Na+

channels also open voltage gated K+ channelDue to slow opening of these channels they open just

at the same time that the Na+ channels are beginning to close because of inactivation.

So now decrease Na+ influx and simultaneous increase in K+ out flux cause membrane potential to go back to resting state (recovery of RMP)

These channels close when membrane potential reaches back to RMP

•.

Phases of action potential

DepolarizationRepolarizationHyperpolarization

Initiation of action potentialTo initiate an AP a triggering event causes the

membrane to depolarize from the resting potential of -90 mvs.

Depolarization proceeds slowly at first until it reaches a critical level known as threshold potential. i.e.

-65 mvs . At threshold explosive depolarization occurs.

An AP will not occur until the initial rise in membrane potential reaches a threshold level.

This occurs when no. of Na+ entering the cell becomes greater than the no. of K+ leaving the cell.

Threshold and Action PotentialsThreshold Voltage– membrane is depolarized by 15 to 20 mV

Subthreshold stimuli produce subthreshold depolarizations and are not translated into APs

Stronger threshold stimuli produce depolarizing currents that are translated into action potentials

All-or-None phenomenon – action potentials either happen completely, or not at all depending on threshold

Action Potential: Resting StateNa+ and K+ channels are closedEach Na+ channel has two voltage-regulated

gates Activation gates –

closed in the resting state

Inactivation gates – open in the resting state

Depolarization opens the activation gate (rapid) and closes the inactivation gate (slower) The gate for the K+ is slowly opened with depolarization.

Depolarization PhaseNa+ activation gates open quickly and Na+ enters causing local depolarization which opens more activation gates and cell interior becomes progressively less negative. Rapid depolarization and polarity reversal.

Threshold – a critical level of depolarization (-55 to -60 mV) where depolarization becomes self-generating

Positive Feedback?

Repolarization Phase Sodium inactivation gates of Na+ channels close.

As sodium gates close, the slow voltage-sensitive K+ gates open and K+ leaves the cell following its electrochemical gradient and the internal negativity of the neuron is restored

Hyperpolarization

The slow K+ gates remain open longer than is needed to restore the resting state. This excessive efflux causes hyperpolarization of the membrane

The neuron is insensitive to stimulus and depolarization during this time

Depolarization increases the probability of producing nerve impulses. Hyperpolarization reduces the probability of producing nerve impulses.

Role of the Sodium-Potassium Pump

Repolarization restores the resting electrical conditions of the neuron, but does not restore the resting ionic conditions

Ionic redistribution is accomplished by the sodium-potassium pump following repolarization

Importance of Action Potential Generation

Nerve traffic, muscle contraction, hormone release, G.I. secretions, Cognitive thought, etc.

Action Potentials are required for the senses - Sight, hearing, and touch are all dependent on action potentials for transmission of information to the brain

Threshold stimuli (Graded Potential) cause the.generation of an action potential

Role of Calcium ions in Action potentialCalcium pump in almost all cells of the body

maintain the calcium gradient with high Ca in ECF as compared to ICF.

In addition to Ca pumps there are voltage gated Ca channels which are slightly permeable to Na+ as well as to Ca++ ions.

So when they open both Na and Ca flow to the interior of the fiber. So called Ca Na channels.

They are slow to open requiring 20 times as long for activation as Na channels so called slow channels in contrast to Na channels which are fast channels.

Ca++ channels are numerous in smooth muscles and cardiac muscle. In some smooth muscles the fast Na+ channels are hardly present so that the AP are caused almost entirely by activation of slow Ca++ channels.

Increased permeability of Na channels when there is deficit of Ca ionsThe conc. Of Ca ions in ECF has profound

effect on the voltage level at which the Na channels become activated.

So when there is a deficit of Calcium ions in the ECF the voltage gated Na channels open by very little increase of MP from its normal very negative level. so nerve fiber become highly excitable .

When Ca levels fall 50% below normal spontaneous discharge occurs in some

peripheral nerves causing tetany. Its lethal when respiratory muscles are involved.

Cause:Ca bind to the exterior surface of the

voltage gated Na channels protein molecule.

The +ve charge of Ca ions in turn alter the electrical state of the channel protein itself.

So altering the voltage level required to open the sodium gates.

Propagation of Action PotentialA single action

potential involves only a small portion of the total excitable cell membrane and then the action potential is self-propagating and moves away from the stimulus (point of origin)

Direction of Action potentialAP travels in all directions away from the

stimulus until the entire membrane is depolarized

Conduction of Action PotentialsTwo types of propagation

Contiguous conductionConduction in unmyelinated fibersAction potential spreads along every portion

of the membraneSaltatory conduction

Rapid conduction in myelinated fibersImpulse jumps over sections of the fiber

covered with insulating myelin

Nerve or muscle impulseThe transmission of the depolarization

process along a nerve or muscle fibre is called impulse

An action potential in the axon of a neuron is called a nerve impulse and is the way neurons communicate.

Parts of neuron and signal transmission in nerve trunks

MyelinationMost mammalian axons are myelinated.The myelin sheath is provided by

oligodendrocytes and Schwann cells.

MYELINMyelin

Primarily composed of lipids sphingomyelinFormed by oligodendrocytes in CNSFormed by Schwann cells in PNS

• Myelin is insulating, preventing passage of ions over the membrane as it is made up of lipids so water soluble ions cannot permeate so current cannot leak out in the ECF

Myelination

In PNS each Schwann cell myelinates 1mm of 1 axon by wrapping round & round axonElectrically

insulates axon

• The resistance of the membrane to current leak out of the cell and the diameter of the axon determine the speed of AP conduction.

• Large diameter axons provide a low resistance to current flow within the axon and this in turn, speeds up conduction.

•Myelin sheath which wraps around vertebrate axons prevents current leak out of the cells. Acts like an insulator, for example, plastic coating surrounding electric wires. It is devoid of any passage ways.

• However, portions of the axons lack the myelin sheath and these are called Nodes of Ranvier. They are present at about 1 mm intervals along the length of axons . High concentration of Na+ channels are found at these nodes so AP occurs only at nodes

2 ways to increase AP propagation speed

Saltatory Conduction (Saltere means jump or leap)

• When depolarization reaches a node, Na+ enters the axon through open channels.

• At the nodes, Na+ entry reinforces the depolarization to keep the amplitude of the AP constant

• However, it speeds up again when the depolarization encounters the next node.

•The apparent leapfrogging of APs from node to node along the axon is called saltatory conduction.

•Myelinated fibers conduct impulses about 50 times faster than unmyelinated fibers of comparable size

F8-22

•Saltatory conduction in myelinated fibers from node to node

•As no ions can flow through myelin sheath they can flow with ease through node of ranvier.

•Therefore, action potential or flow of electrical currents occurs from node to node in a jumping manner known as saltatory conduction

Importance of saltatory conduction

•Increases the conduction velocity through myelinated nerve fiber.•Conserves energy for the axon

Multiple Sclerosis

• In demylinating diseases, such as multiple sclerosis, the loss of myelin in the nervous system slows down the conduction of APs. Multiple sclerosis patients complain of muscle weakness, fatigue, difficulty with walking

Plateau in some action potentialsIn cardiac muscle the excited muscle

membrane does not repolarize immediately after depolarization ; instead the potential remains on a plateau near the peak of the spike potential only then does repolarization begins.

Plateau prolongs the period of depolarization so prolongs the contraction of heart muscle

Cause of plateauIt is due to combination of factors:

1)First two types of channels causes depolarization

a)Voltage gated Na+ channels called fast channels for spike potential

b)Slow Ca++ Na+ channels for plateau portion

2) The voltage gated K+ channels are slower than usual to open, often not opening until the end of plateau this delays the return of the MP towards normal resting value

•.

The Action Potential Types

Rhythmicity of some excitable tissuesRepetitive self induced discharges occurs

normally in the heart , in most smooth muscles and in neurons of the CNS.

The rhythmical discharges causes:1.Rhythmical beat of the heart2.Rhythmical peristalsis of intestine3.Rhythmical control of respiration

Re- excitation process necessary for spontaneous rhythmicityFor spontaneous rhythmicity to occur, the

membbrane even in its natural state must be permeable enough to Na + ions or to Ca and Na thru slow channels

The resting membrane potential in the rhythmical control center of the heart is only -60 - -70mvs

This is not enough –ve voltage to keep the Na and Ca channels totally closed .

So following sequence of events take place:1.Some Na and Ca ions flow inside2.This increases the membrane voltage in +ve

direction which further increases membrane permeability .

3.Still more ions flow inside4.+ve feed back mechanism5.AP is generated6.Then membrane repolarizes7.Again depolarization and new AP8.This cycle repeats again and again & causes

self induced rhythmical excitation of the excitable tissue

RHYTHMICITY IN EXICATABLE TISSUESRHYTHMICITY IN EXICATABLE TISSUES

REPETITIVE,SPONTANEOUS AND SELF INDUCED DISCHARGE

RHYTHIMICITY OCCUR IN HEART PACEMAKER, PERISTALSIS OF INTESTINE etc

Chapter 4 Principles of Neural and Hormonal CommunicationHuman Physiology by Lauralee Sherwood ©2010 Brooks/Cole, Cengage Learning

Graded Potential vs Action Potential

Principles of Action Potentials1. The All or Nothing Principle:

Action Potentials occur in all or none fashion depending on the strength of the stimulus

2. The Refractory Period:Responsible for setting up limit on the frequency of Action Potentials

All-or-None Principle

• If any portion of the membrane is depolarized to threshold an AP is initiated which

will go to its maximum height.• A triggering event stronger than one necessary

to bring the membrane to threshold does not produce a large AP.

• However a triggering event that fails to depolarize the membrane to threshold does not trigger the AP at all.

All or none principleThus an excitable membrane either respond

to a triggering event with maximal Action potential that spread throughout the membrane in a non decremental manner or it does not respond with an AP at all. This is called all or non law.

ImportanceThe importance of threshold

phenomenon is that it allows some discrimination b/w important and unimportant stimuli . Stimulus too weak to bring the membrane potential to threshold do not initiate action potentials and therefore do not transmit the signals.

Refractory period (unresponsive or stubborn)A new action potential cannot occur in an excitable membrane as long as the membrane is still depolarized from the preceding action potential.

Refractory PeriodsAbsolute refractory

period: Membrane cannot produce

another AP because Na+ channels are inactivated and no amount of excitatory signal applied to these channels at this point will open the inactivation gates.

Relative refractory period occurs when VG K+ channels are open, making it harder to depolarize to threshold 7-38

Absolute Refractory Period

The absolute refractory period is the time from the opening of the Na+ activation gates until the closing of inactivation gates

When a section of membrane is generating an AP and Na+ channels are open, the neuron cannot respond to another stimulus

Relative Refractory PeriodThe relative refractory period is the interval following the absolute refractory period when:

Na+ gates are closed

K+ gates are open

Repolarization is occurring

During this period, the threshold level is elevated, allowing only strong stimuli to generate an AP (a strong stimulus can cause more frequent AP generation) a large suprathreshold graded potential can start a second AP by activating Na+ channels which have been reset

• Absolutely refractory period- a second AP will not occur until the first is over. The gates on the Na+ channel have not reset.

•Relatively refractory period- a large suprathreshold graded potential can start a second AP by activating Na+ channels which have been reset.

Refractory Periods Limit the Frequency of APs

F8-17

Significance of refractory periodBy the time the original site has recovered

from its refractory period and is capable of being restimulated by normal current flow the AP has been rapidly propagated in forward direction only and is so far away that it no longer influence the original site so ensure one way propagation of the action potential

• Refractory periods limit the rate at which signals can be transmitted down a neuron. Limit is around 100 impulses/s.

• The greater the RP the greater the delay before a new AP can be initiated and lower the frequency with which a nerve cell can respond to repeated or on going stimulation

Refractory Periods Limit the Frequency of APs

Refractory Periods

Frequency of Action Potential Firing is Proportional to the Size of the Graded

Potential

The amount of neurotransmitter released from the axon terminal is proportional to the frequency of action potentials.

F8-18

Factors Affecting Excitability of Nerve

1-Increase excitability:1-Increase excitability:

-Increase Na permeability (Depolarize):-Increase Na permeability (Depolarize):Low extracellularLow extracellular Ca++

--Increase extracellularIncrease extrac K concentration..2-Decrease excitability (membrane stabilizers)2-Decrease excitability (membrane stabilizers)

--Decreased Na permeability:Decreased Na permeability:High extracellularHigh extracellular, Ca++ and local anesthesia

--Decrease extracellularDecrease extracellular K+ concentration. .

•Membrane stabilizers :

•In addition to the factors that increases membrane excitability still others which decreases excitability of the membrane called membrane stabilizing factors.

•For e.g. high ECF Ca++ decreases membrane permeability to Na+ and simultaneously reduces excitability so Ca++ are said to be a membrane stabilizer

•Local anesthetics: they r also membrane stabilizers. E.g. procaine and tetracaine. They act directly on the activation gates of Na++ making it much more difficult for these gates to open so reducing membrane excitability.

•Graded potential Action PotentialMay be positive (depolarize) always begin with dep.Or negative (hyperpolarize)

Graded: proportional to stimulus All or noneStrength

Reversible, returns to RMP if stimulation Irreversible: goes to Ceases before threshold is reached completion once it beginLocal: has effect for only short distance generalDecremental: signal grows weaker Non decrementalwith distance