Wheeler D D, Edwards A M, Ondo J G
Department of Physiology, Medical University of South Carolina, Charleston 29425.
Neuropharmacology. 1993 Feb;32(2):195-204. 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(-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.
已在含有低或高[Na]的缓冲液中测量了可卡因对突触体膜电位（Em）、对藜芦碱诱导的膜去极化或高[K]o诱导的膜去极化以及对钠/钾渗透率比值（pNa/pK）的影响。使用罗丹明6G染料的荧光来测量膜电位。在低[Na]缓冲液中，可卡因在浓度介于10⁻⁶和10⁻⁵ M之间时开始降低Em（去极化），在高[Na]缓冲液中则在浓度介于10⁻⁵和10⁻⁴ M之间时开始降低Em。最大去极化（使用10⁻³ M可卡因时）在低[Na]缓冲液中为21 mV，在高[Na]缓冲液中为11 mV。可卡因还降低了藜芦碱或高[K]o引起的去极化；可卡因降低对藜芦碱反应的有效浓度是降低对高[K]o反应所需浓度的十分之一。可卡因对藜芦碱反应的拮抗作用与其他研究者发现的相似；然而，这种作用倾向于对抗去极化，因此无法单独解释可卡因的去极化作用。可卡因对高[K]引起的去极化的拮抗作用与pK降低一致；pK的这种变化可以解释仅由可卡因引起的观察到的Em降低。还测量了可卡因（10⁻³ M）对Em的影响，作为低和高[Na]o时[K]o的函数。可卡因在所有[K]o值下（3.9 - 19.2 mV）均引起膜去极化，在低[Na]介质中的这种效应稍大。这些Em测量值符合戈德曼方程，并估计了pNa/pK比值。可卡因的存在使pNa/pK的估计值增加了45.7%，可能是通过降低pK实现的。
