Electrophysiology

Dr Mohammed Haroon Rashid, MD

OUTLINE

Resting Membrane Potential Definitions and Normal value Ionic basis Action Potentials Definition Ionic basis depolarization, repolarization, hyperpolarization Characteristics Propagation of Action Potentials Local Potentials

Membrane Potentials caused by Diffusion

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

Nernst Potential

The diffusion potential across a membrane that exactly opposes the net diffusion of a particular ion through the membrane Determined by the ratio of the concentrations of that specific ion on the two sides of the membrane EMF = 61 log concentration inside concentration outside

Nernst Potential
Assumptions The potential in the ECF outside is zero The Nernst potential is the potential inside the membrane The sign of the potential is (+) if the diffusing ion is negative The sign of the potential is (-) if the diffusing ion is positive

Ion Channels
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Are integral proteins that span the membrane and when open permit the passage of proteins Ion channels are selective Ion channels maybe or open or closed The conductance of a channel is dependent on the probability that the channel is open or closed

Ion Channels
1. Voltage Gated Channels - Controlled by changes in membrane potential 2. Ligand gated channels Opened or closed by hormone, neurotransmitters, and second messengers

Diffusion Potential

Potential difference generated across a membrane because of a concentration difference of an ion Generated only if the membrane is permeable to the ion Depends on the 1) concentration of ions, 2) permeability of the membrane and 3) polarity of the charge of each ion

Diffusion Potential
Goldman Equation > Gives the calculated membrane potential on the inside of the membrane > EMF = 61log CNa iPNa+ CK iPK + CCl oPCl CNa oPNa+ CK oPK + CCl iPCl

Diffusion Potential
Goldman Equation Na, K, Cl are the most important ions in the development of the membrane potential The degree of importance of each of the ions in determining the voltage is proportional to the membrane permeability

Diffusion Potential
Goldman Equation A positive ion concentration gradient from inside the membrane to the outside causes electronegativity inside the membrane Na and K channels undergoes rapid changes during transmission of a nerve impulse; Cl channels does not change greatly

Resting Membrane Potential

- -90millivolts Na-K Pump An electrogenic pump - more positive charges are pumped to the outside (3 Na out: 2 K in) causing a negative potential inside An active metabolic process Strongly stimulated when excess Na accumulate inside the membrane

Resting Membrane Potential

K-Na leak Channels K ions leak outside Channels are 100x more permeable to K

Resting Membrane Potential

Normal Factors in the Establishment of the Normal Resting Membrane Potential K Diffusion Potential - K ions inside to outside 35:1 Na Diffusion through the membrane Na-K Pump

Voltage Gated Na Channels

Activation of Na channels -70 to -50 mV causes conformational change opening the gate Na ions then go inwards, increasing Na permeability 500 to 5000 fold

Voltage Gated Na Channels

Inactivation of Na channels Slower process Membrane potential begins to recover repolarization Will not reopen until the membrane potential returns to normal

Voltage Gated K Channels

Activation of K Channels Opens when the membrane potential approaches zero Allows increased diffusion of K outside Combines with delayed closure of Na channels to speed repolarization

Nerve Action Potential

Stages Resting Stage - Normal polarized state of -90mV Depolarization Stage - Increased Na permeability to the inside - Overshoot phenomenon Repolarization Stage - Na channels close and K channels open

Nerve Action Potential

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2. 3.

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Definitions Depolarization makes the membrane potential less negative Hyperpolarization makes the membrane potential become more negative Inward Current flow of positive charge into the cell Outward Current flow of positive charge out of the cell

Nerve Action Potential

Definitions 5. Threshold is the membrane potential in which an action potential is inevitable 6. Action Potential property of excitable cells that consist of a rapid depolarization, followed by repolarization. They have stereotypical size and shape, are propagating and are all or none

Events that Cause an Action Potential

At rest, the conductance for K ions is 50- 100x greater than Na (K leak channels) At the onset of action potential, Na channels (5000x Na conductance) and K channels (opening more slowly) become activated At the end of the action potential, return of the membrane potential to the negative state

Role of Other Ions

Anions Responsible for the negative charge during net deficit of positively charged ions Ca Ions Ca pump - pumps Ca from the interior to the exterior Ca- Na channels slow channels; Na and Ca to the interior Hypocalcemia Na channels become easily activated or highly excitable; tetany

Initiation of the Action Potential

Positive Feedback Vicious Cycle Threshold for Initiation Na ions entering > K ions exiting Sudden rise of 15-30 millivolts is required -65 millivolts, threshold for stimulation

Propagation of Action Potential

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2.

Nerve or Muscle Impulse transmission of depolarization process along a nerve or muscle fiber Has no single direction All or nothing principle Plateau in action potentials Caused by fast and slow channels Voltage gated K channels

Propagation of Action Potential

Occurs by the spread of local currents to adjacent areas of membrane Conduction Velocity is increased by: Increased fiber size Myelination saltatory conduction

Refractory Periods

Absolute Refractory Period Period in which another action potential cannot be elicited no matter how large the stimulus Caused by the closed inactivation gates of the Na channels No action potential can be generated until the inactivation gates open

Refractory Periods

Relative Refractory Period An action potential can be elicited during this period only if a larger than usual inward current is provided Caused by the higher K conductance than at rest, therefore is farther from the threshold

Refractory Periods

Accommodation The cell membrane is held at a depolarized level such that the threshold potential is passed without firing an action potential Seen in hyperkalemia

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