Ionic Blockage of Sodium Channels in Nerve

Ionic Blockage of Sodium Channels in Nerve

VOLUME 61, 1973 | ANN M. WOODHULL
This paper investigates the effect of hydrogen ions (H+) on sodium currents in frog nerve fibers. The study finds that increasing the pH of the bathing medium reversibly reduces sodium permeability, with the reduction being more pronounced at more positive membrane potentials. The depression in sodium permeability is attributed to the voltage-dependent blockage of sodium channels by H+ ions, which enter the open channel and bind there, preventing sodium ion passage. The model assumes that the binding site is located far enough across the membrane for the bound ions to be affected by the membrane potential. Equations are derived to describe the general case where the blocking ion enters the channel from either side of the membrane. For H+ ion blockage, a simpler model is proposed, where H+ ions enter the channel only from the bathing medium. The dissociation constant of H+ ions from the channel site is found to be 9.9 × 10−6 M (pKa 5.4), similar to that of a carboxylic acid. The voltage dependence of the block suggests that the acid site is about one-quarter of the way across the membrane potential from the outside. In addition to blocking, H+ ions also shift the responses of sodium channel "gates" to voltage, likely by altering the surface potential of the nerve. The paper also presents evidence for voltage-dependent blockage by calcium ions. The results support the idea that the sodium channel has an acidic group inside, which is crucial for the observed effects.This paper investigates the effect of hydrogen ions (H+) on sodium currents in frog nerve fibers. The study finds that increasing the pH of the bathing medium reversibly reduces sodium permeability, with the reduction being more pronounced at more positive membrane potentials. The depression in sodium permeability is attributed to the voltage-dependent blockage of sodium channels by H+ ions, which enter the open channel and bind there, preventing sodium ion passage. The model assumes that the binding site is located far enough across the membrane for the bound ions to be affected by the membrane potential. Equations are derived to describe the general case where the blocking ion enters the channel from either side of the membrane. For H+ ion blockage, a simpler model is proposed, where H+ ions enter the channel only from the bathing medium. The dissociation constant of H+ ions from the channel site is found to be 9.9 × 10−6 M (pKa 5.4), similar to that of a carboxylic acid. The voltage dependence of the block suggests that the acid site is about one-quarter of the way across the membrane potential from the outside. In addition to blocking, H+ ions also shift the responses of sodium channel "gates" to voltage, likely by altering the surface potential of the nerve. The paper also presents evidence for voltage-dependent blockage by calcium ions. The results support the idea that the sodium channel has an acidic group inside, which is crucial for the observed effects.
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