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

Effects of cocaine on the synaptosomal membrane potential (Em), on membrane depolarization induced by veratridine or elevated [K]. 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(-3) M) 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.