The effect of cocaine on membrane potential, on membrane depolarization by veratridine or elevated [K] o and on sodium/potassium permeability ratios in synaptosomes from the limbic cortex of the rat

• Published in: Neuropharmacology Vol. 32; no. 2; pp. 195 - 204
• Main Authors: Wheeler, D.D., Edwards, A.M., Ondo, J.G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.1993
• Subjects: Animals; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; cocaine; Cocaine - pharmacology; Fluorescence; In Vitro Techniques; ion permeabilities; Limbic System - drug effects; Limbic System - metabolism; Male; membrane potential; Membrane Potentials - drug effects; Nerve Endings - drug effects; Neuromuscular Depolarizing Agents - pharmacology; Potassium - metabolism; Potassium - pharmacology; Rats; Rats, Sprague-Dawley; Sodium - metabolism; Synaptic Membranes - drug effects; synaptosomes; Synaptosomes - drug effects; Synaptosomes - metabolism; Veratridine - antagonists & inhibitors; Veratridine - pharmacology; ion permeabilities; cocaine; synaptosomes; membrane potential
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/0028-3908(93)90100-H

Effects of cocaine on the synaptosomal membrane potential ( Em), on membrane depolarization induced by veratridine or elevated [K] o and on sodium/potassium permeability ratios (pNa/pK), have been measured in buffer containing either low or high [Na]. Fluorescence of the dye rhodamine 6G was used to measure the membrane potential. Cocaine began to reduce the Em (depolarized) at concentrations between 10 −6 and 10 −5 M in low [Na] buffer and between 10 −5 and 10 −4 M in high [Na] buffer. Maximum depolarization (with 10 −3 M cocaine) was 21 mV in low [Na] buffer and 11 mV in high [Na] buffer. Cocaine also reduced the depolarization caused by veratridine or elevated [K] o; the effective concentration of cocaine in reducing the response to veratridine was one-tenth that necessary to reduce the response to elevated [K] o. The antagonism by cocaine of the response to veratridine was similar to that found by other investigators; however, this action would tend to oppose depolarization and thus cannot explain the depolarizing effect of cocaine alone. The antagonism by cocaine of the depolarization caused by elevated [K] was consistent with a reduction in pK; such a change in pK could explain the observed reduction in Em caused by cocaine alone. The effect of cocaine (10 −3M) on the Em was also measured as a function of [K] o at low and high [Na] o. Cocaine caused membrane depolarization at all [K] o's (3.9−19.2 mV), an effect that was somewhat greater in the low [Na] medium. These measurements of Em were fitted to the Goldman equation and the ratio of pNa/pK estimated. The presence of cocaine increased the estimate of pNa/pK by 45.7%, presumably by reducing pK.