0573Electrophysiology.ppt

ElectrophysiologElectrophysiologyy

Dr Mohammed Haroon Dr Mohammed Haroon Rashid, MDRashid, MD

OUTLINEOUTLINE Resting Membrane PotentialResting Membrane Potential- Definitions and Normal valueDefinitions and Normal value- Ionic basisIonic basis Action PotentialsAction Potentials- DefinitionDefinition- Ionic basis – depolarization, Ionic basis – depolarization,

repolarization, hyperpolarizationrepolarization, hyperpolarization- CharacteristicsCharacteristics Propagation of Action PotentialsPropagation of Action Potentials Local PotentialsLocal Potentials

Membrane Potentials Membrane Potentials caused by Diffusioncaused by Diffusion

K concentration inside > outsideK concentration inside > outside -94 millivolts -94 millivolts diffusion potential of Kdiffusion potential of K Na concentration outside > insideNa concentration outside > inside +61 millivolts +61 millivolts diffusion potential of diffusion potential of

NaNa

Nernst PotentialNernst Potential

The diffusion potential across a The diffusion potential across a membrane that exactly opposes the net membrane that exactly opposes the net diffusion of a particular ion through the diffusion of a particular ion through the membrane membrane

Determined by the ratio of the Determined by the ratio of the concentrations of that specific ion on the concentrations of that specific ion on the two sides of the membranetwo sides of the membrane

EMF = EMF = ±61 log log concentration inside concentration inside concentration concentration outsideoutside

Nernst PotentialNernst Potential

AssumptionsAssumptions The potential in the ECF outside is The potential in the ECF outside is

zerozero The Nernst potential is the potential The Nernst potential is the potential

inside the membraneinside the membrane The sign of the potential is (+) if the The sign of the potential is (+) if the

diffusing ion is negativediffusing ion is negative The sign of the potential is (-) if the The sign of the potential is (-) if the

diffusing ion is positivediffusing ion is positive

Ion ChannelsIon Channels

- Are integral proteins that span the Are integral proteins that span the membrane and when open permit the membrane and when open permit the passage of proteinspassage of proteins

Ion channels are selectiveIon channels are selective Ion channels maybe or open or closedIon channels maybe or open or closed The conductance of a channel is The conductance of a channel is

dependent on the probability that the dependent on the probability that the channel is open or closedchannel is open or closed

Ion ChannelsIon Channels

1. Voltage Gated Channels1. Voltage Gated Channels

- Controlled by changes in membrane - Controlled by changes in membrane potentialpotential

2. Ligand gated channels2. Ligand gated channels- Opened or closed by hormone,Opened or closed by hormone,

neurotransmitters, and second neurotransmitters, and second messengersmessengers

Diffusion PotentialDiffusion Potential

Potential difference generated Potential difference generated across a membrane because of a across a membrane because of a concentration difference of an ionconcentration difference of an ion

Generated only if the membrane is Generated only if the membrane is permeable to the ionpermeable to the ion

Depends on the 1) concentration of Depends on the 1) concentration of ions, 2) permeability of the ions, 2) permeability of the membrane and 3) polarity of the membrane and 3) polarity of the charge of each ioncharge of each ion


Goldman EquationGoldman Equation

> Gives the calculated membrane > Gives the calculated membrane potential on the inside of the potential on the inside of the membranemembrane

> EMF = 61log> EMF = 61log C CNa Na iiPPNaNa+ C+ CK K iiPPKK + C + CCl Cl

ooPPClCl

CCNa Na ooPPNaNa+ C+ CK K ooPPKK + C + CCl Cl

iiPPClCl


Goldman EquationGoldman Equation Na, K, Cl are the most important Na, K, Cl are the most important

ions in the development of the ions in the development of the membrane potentialmembrane potential

The degree of importance of each of The degree of importance of each of the ions in determining the voltage the ions in determining the voltage is proportional to the membrane is proportional to the membrane permeabilitypermeability


Goldman EquationGoldman Equation A positive ion concentration gradient A positive ion concentration gradient

from inside the membrane to the from inside the membrane to the outside causes electronegativity outside causes electronegativity inside the membraneinside the membrane

Na and K channels undergoes rapid Na and K channels undergoes rapid changes during transmission of a changes during transmission of a nerve impulse; Cl channels does not nerve impulse; Cl channels does not change greatly change greatly

Resting Membrane Resting Membrane PotentialPotential

- -90millivolts- -90millivolts Na-K PumpNa-K Pump An An electrogenic pump electrogenic pump - more positive - more positive

charges are pumped to the outside (3 charges are pumped to the outside (3 Na out: 2 K in) causing a negative Na out: 2 K in) causing a negative potential insidepotential inside

An active metabolic processAn active metabolic process Strongly stimulated when excess Na Strongly stimulated when excess Na

accumulate inside the membraneaccumulate inside the membrane


K-Na leak ChannelsK-Na leak Channels K ions “leak” outsideK ions “leak” outside Channels are 100x more permeable Channels are 100x more permeable

to K to K


Normal Factors in the Establishment Normal Factors in the Establishment of the Normal Resting Membrane of the Normal Resting Membrane PotentialPotential

K Diffusion PotentialK Diffusion Potential

- K ions inside to outside 35:1- K ions inside to outside 35:1 Na Diffusion through the membraneNa Diffusion through the membrane Na-K PumpNa-K Pump

Voltage Gated Na Voltage Gated Na ChannelsChannels

Activation of Na channelsActivation of Na channels -70 to -50 mV causes -70 to -50 mV causes

conformational change opening the conformational change opening the gategate

Na ions then go inwards, increasing Na ions then go inwards, increasing Na permeability 500 to 5000 foldNa permeability 500 to 5000 fold

Voltage Gated Na Voltage Gated Na ChannelsChannels

Inactivation of Na channelsInactivation of Na channels Slower processSlower process Membrane potential begins to Membrane potential begins to

recover – recover – repolarizationrepolarization Will not reopen until the membrane Will not reopen until the membrane

potential returns to normalpotential returns to normal

Voltage Gated K Voltage Gated K ChannelsChannels

Activation of K ChannelsActivation of K Channels Opens when the membrane potential Opens when the membrane potential

approaches zeroapproaches zero Allows increased diffusion of K Allows increased diffusion of K

outsideoutside Combines with delayed closure of Combines with delayed closure of

Na channels to speed repolarizationNa channels to speed repolarization

Nerve Action PotentialNerve Action Potential

StagesStages Resting StageResting Stage

- Normal polarized state of -90mV- Normal polarized state of -90mV Depolarization StageDepolarization Stage- Increased Na permeability to the Increased Na permeability to the

insideinside- Overshoot phenomenonOvershoot phenomenon Repolarization StageRepolarization Stage

- Na channels close and K channels open- Na channels close and K channels open


DefinitionsDefinitions1.1. Depolarization – makes the Depolarization – makes the

membrane potential less negativemembrane potential less negative2.2. Hyperpolarization – makes the Hyperpolarization – makes the

membrane potential become more membrane potential become more negativenegative

3.3. Inward Current – flow of positive Inward Current – flow of positive charge into the cellcharge into the cell

4.4. Outward Current – flow of positive Outward Current – flow of positive charge out of the cellcharge out of the cell


DefinitionsDefinitions

5. Threshold – is the membrane potential 5. Threshold – is the membrane potential in which an action potential is inevitablein which an action potential is inevitable

6. Action Potential – property of excitable 6. Action Potential – property of excitable cells that consist of a rapid cells that consist of a rapid depolarization, followed by depolarization, followed by repolarization. They have stereotypical repolarization. They have stereotypical size and shape, are propagating and are size and shape, are propagating and are all or noneall or none

Events that Cause an Action Events that Cause an Action PotentialPotential

At rest, the conductance for K ions is 50- At rest, the conductance for K ions is 50- 100x greater than Na (K leak channels)100x greater than Na (K leak channels)

At the onset of action potential, Na At the onset of action potential, Na channels (5000x Na conductance) and K channels (5000x Na conductance) and K channels (opening more slowly) become channels (opening more slowly) become activatedactivated

At the end of the action potential, return At the end of the action potential, return of the membrane potential to the of the membrane potential to the negative statenegative state

Role of Other IonsRole of Other Ions AnionsAnions Responsible for the negative charge Responsible for the negative charge

during net deficit of positively charged during net deficit of positively charged ionsions

Ca IonsCa Ions Ca pump - pumps Ca from the interior Ca pump - pumps Ca from the interior

to the exteriorto the exterior Ca- Na channelsCa- Na channels – slow channels; Na – slow channels; Na

and Ca to the interiorand Ca to the interior Hypocalcemia –Hypocalcemia –Na channels become Na channels become

easily activated or highly excitable; easily activated or highly excitable; tetanytetany

Initiation of the Action Initiation of the Action PotentialPotential

Positive Feedback Vicious CyclePositive Feedback Vicious Cycle Threshold for InitiationThreshold for Initiation Na ions entering > K ions exitingNa ions entering > K ions exiting Sudden rise of Sudden rise of 15-30 millivolts15-30 millivolts is is

requiredrequired -65 millivolts, -65 millivolts, threshold for threshold for

stimulation stimulation

Propagation of Action Propagation of Action PotentialPotential

Nerve or Muscle Impulse – Nerve or Muscle Impulse – transmission of depolarization transmission of depolarization process along a nerve or muscle fiberprocess along a nerve or muscle fiber

Has no single directionHas no single direction All or nothing principle All or nothing principle Plateau in action potentialsPlateau in action potentials

1.1. Caused by fast and slow channelsCaused by fast and slow channels

2.2. Voltage gated K channelsVoltage gated K channels

Propagation of Action Propagation of Action PotentialPotential

Occurs by the spread of local Occurs by the spread of local currents to adjacent areas of currents to adjacent areas of membranemembrane

Conduction Velocity is increased by:Conduction Velocity is increased by: Increased fiber sizeIncreased fiber size Myelination – Myelination – saltatory conductionsaltatory conduction

Refractory PeriodsRefractory Periods

Absolute Refractory PeriodAbsolute Refractory Period- Period in which another action Period in which another action

potential cannot be elicited no potential cannot be elicited no matter how large the stimulusmatter how large the stimulus

- Caused by the closed inactivation Caused by the closed inactivation gates of the Na channelsgates of the Na channels

- No action potential can be generated No action potential can be generated until the inactivation gates openuntil the inactivation gates open


Relative Refractory PeriodRelative Refractory Period- An action potential can be elicited An action potential can be elicited

during this period only if a larger during this period only if a larger than usual inward current is than usual inward current is providedprovided

- Caused by the higher K conductance Caused by the higher K conductance than at rest, therefore is farther than at rest, therefore is farther from the thresholdfrom the threshold


AccommodationAccommodation- The cell membrane is held at a The cell membrane is held at a

depolarized level such that the depolarized level such that the threshold potential is passed without threshold potential is passed without firing an action potentialfiring an action potential

- Seen in Seen in hyperkalemiahyperkalemia

Thank You!!!Thank You!!!

Documents

0573Electrophysiology.ppt