Molecular Pharmacology, Vol 20, 98-106, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Quinidine Interactions with Myxicola Giant Axons

¹ Laboratory of Biophysics, Intramural Research Program, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20205

The effects of quinidine, an antiarrhythmic alkaloid, on the membrane conductances of Myxicola axonal membrane were investigated by using the voltage-clamp technique. In the presence of 0.2 mM quinidine sulfate, the resting membrane potential was not affected, whereas the repolarization phase of the action potential was prolonged. Under voltage-clamp conditions, potassium currents displayed a distinct peak before decaying exponentially to a plateau level. Both sodium and potassium conductances were suppressed. However, the potassium conductance was suppressed to a much greater extent and displayed a negative slope in the conductance-voltage curve for membrane potentials above +40 mV. The kinetics of sodium currents were not appreciably affected. The block of potassium channels by quinidine displayed both time- and voltage-dependent characteristics. The percentage of reduction in current depended upon the fraction of the potassium channels open under control conditions. Quinidine blocked both outward and inward potassium currents. The block was less in the presence of high external potassium ions. Two-pulse experiments showed that the number of "inactivated" potassium channels was dependent upon the prepulse potential. Recovery from inactivation was enhanced by hyperpolarization. The primary effect of quinidine in Myxicola was attributed to a quinidine-induced block of potassium conductance.

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ACKNOWLEDGMENTS The author thanks Drs. G. Ehrenstein, M. Huang, H. Lecar, and N. Moran for their thorough reading of the manuscript and their suggestions and Dr. R. Fitzhugh for the use of his computer programs to transfer data to the DEC-10 computer of Division of Computer Research and Technology at the National Institutes of Health for analysis with Modeling Laboratory.