Introduction to physiology Your colleague, Firas alkhalayleh Your colleague, Firas alkhalayleh A 3’rd year medical student A 3’rd year medical student

Nerve and Muscle Physiology Plasma Membranes of Excitable tissues Plasma Membranes of Excitable tissues Ref: Guyton, 12 th ed: pp: th ed: p57-71, Ref: Guyton, 12 th ed: pp: th ed: p57-71,

Resting membrane potential Resting membrane potential

{NA+} inside = 14 mEq/L {NA+} inside = 14 mEq/L {Na+} outside = 142 mEq/L {Na+} outside = 142 mEq/L {K+} inside = 140 mEq/L {K+} inside = 140 mEq/L {K+} outside = 4 mEq/L {K+} outside = 4 mEq/L

The diffusion potential for K+ only is found to be -94 millivolte The diffusion potential for K+ only is found to be -94 millivolte The diffusion potential for Na+ only is found to be +61 millivolte The diffusion potential for Na+ only is found to be +61 millivolte

Nernest equation E (mV) = - 61.log (Ci/Co) E = Equilibrium potential for a univalent ion. Ci = conc. inside the cell. Co = conc. outside the cell.

The greater the ratio {I}/{o}, the greater tendency to diffuse in one direction. The greater the ratio {I}/{o}, the greater tendency to diffuse in one direction. At normal body tempreture At normal body tempreture EMF=+/- 61 * log {I}/{O} EMF= electromotive force.

Nernst equation means ……. !!!! Nernst equation means ……. !!!! If EMF is + the moving ions are – If EMF is + the moving ions are – If EMF is - the moving ions are + If EMF is - the moving ions are +

Multiple ions involvement Depends on : Depends on : 1. Polarity of the electrical charges. 2. Permeability of the membrane. 3. The {I} + {O}

Goldman-Hodgkin-Katz equation EMF (mV) = log [( CiNa+. PNa+ + CiK+. PK+ + CoCl-.PCl- ) log [( CiNa+. PNa+ + CiK+. PK+ + CoCl-.PCl- ) (CoNa+ PNa+ + CoK+ PK+ + CiCl- PCl-)] (CoNa+ PNa+ + CoK+ PK+ + CiCl- PCl-)] Ci = Conc. inside Co = Conc. outside P = permeability of the membrane to that ion.

During transmission of nerve impulses, permeability of the Na+ and K+ undergoes rapid change, whereas that of Cl- doesn't change greatly. During transmission of nerve impulses, permeability of the Na+ and K+ undergoes rapid change, whereas that of Cl- doesn't change greatly.

K+ leak channels are 100 times more permeable to K+ than Na+. K+ leak channels are 100 times more permeable to K+ than Na+.

Action potential A rapid change in the membrane potential. A rapid change in the membrane potential. Resting stage. Resting stage. Depolarization stage. Depolarization stage. Repolarization stage. Repolarization stage.

Voltage-gated channels

When the membrane potential becomes less negative than during the resting state, rising from -90 toward 0, it finally reaches a voltage – usually between -70 and -50 – that cause a sudden conformational change in the activation gate, flipping it all the way to the open position.This is called the activated state, during this state, Na+ ions pour inward through the channel increasing the Na+ permeability of the membrane as much as 500-to 5000-fold. When the membrane potential becomes less negative than during the resting state, rising from -90 toward 0, it finally reaches a voltage – usually between -70 and -50 – that cause a sudden conformational change in the activation gate, flipping it all the way to the open position.This is called the activated state, during this state, Na+ ions pour inward through the channel increasing the Na+ permeability of the membrane as much as 500-to 5000-fold.

The inactivation state The same increas in the voltage that open the activation gate also closes the inactivation gate. The inactivation gate, however, closes a few 10,000ths of a second after the activation gate opens. That is, the conformational change that flips the inactivation to the closed state is a slower process than the conformational change that opens the activation gate. Therefore after the Na+ channel has remained open for a few 10,000ths of a second, the inactivation gate closes, and the Na+ no longer can pour to the inside of the membrane. At this point, the membrane potential begins to recover back toward the resting state, which is repolartization state. The same increas in the voltage that open the activation gate also closes the inactivation gate. The inactivation gate, however, closes a few 10,000ths of a second after the activation gate opens. That is, the conformational change that flips the inactivation to the closed state is a slower process than the conformational change that opens the activation gate. Therefore after the Na+ channel has remained open for a few 10,000ths of a second, the inactivation gate closes, and the Na+ no longer can pour to the inside of the membrane. At this point, the membrane potential begins to recover back toward the resting state, which is repolartization state.

Voltage –gated K+ channels

During the resting state, the gate of the K+ channel is closed and K+ are prevented from passing to the exterior. When the membrane potential rises from -90 toward 0, this voltage causes a conformational opening of the gate. However, because of the slight delay in the opening of the K+ channel, for the most part, they open just at same time that the Na+ channels are beginning to close because of inactivation. Thus, the decrease in Na+ entry to the cell and the simultaneous increase in K+ exit from the cell combine to speed the repolarization process, leading to full recovery of the RMP. During the resting state, the gate of the K+ channel is closed and K+ are prevented from passing to the exterior. When the membrane potential rises from -90 toward 0, this voltage causes a conformational opening of the gate. However, because of the slight delay in the opening of the K+ channel, for the most part, they open just at same time that the Na+ channels are beginning to close because of inactivation. Thus, the decrease in Na+ entry to the cell and the simultaneous increase in K+ exit from the cell combine to speed the repolarization process, leading to full recovery of the RMP.

The plateau in some APs

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