Jan 1, 1976

Mechanism of action of quinidine on squid axon membranes

The Journal of Pharmacology and Experimental Therapeutics
J Z Yeh, T Narahashi


The mechanism of action of quinidine on squid axons has been examined by means of voltage clamp and internal perfusion techniques. When applied either externally or internally, quinidine HCl suppresses both sodium and potassium conductance increases, the effect on the former accounting for the observed decrease in action potential. The potassium conductance in quinidine undergoes a marked inactivation in a manner dependent upon the membrane potential and time, accounting for the observed prolongation of the terminal falling phase of the action potential. Quinidine methiodide exhibits the effect similar to that of quinidine HCl only when applied internally. The dissociation constants of quinidine in suppressing the sodium conducting system are estimated to be 2.4 x 10(-4) and 4.0 x 10(-4) M for quinidine HCl and methiodide, respectively. The dissociation constant of quinidine in suppressing the potassium-conducting system decreases with increasing step depolarization. When applied externally to the intact axons, quinidine HCl is more effective at external pH 8.6 than at 7.3. When perfused internally, quinidine HCl is more effective at internal pH 7.0 than at 8.0, and the potency is related to the calculated internal concentratio...Continue Reading

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Mentioned in this Paper

Tissue Membrane
Electric Conductivity
Nerve Impulses
Dose-Response Relationship, Drug
Hydrogen-Ion Concentration

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