Convulsant doses of penicillin shorten the lifetime of GABA‐induced channels in cultured central neurones

Abstract

The influence of sodium benzylpenicillin (PCN) on membrane channels activated by gamma-aminobutyric acid (GABA) was studied in cultured spinal neurones of the mouse by the extracellular patch clamp technique. In whole-cell, current clamp recordings, concentrations of PCN above 0.2 mM significantly reduced the amplitude of the GABA response. Single channel currents activated by GABA were studied in outside-out patches of neuronal membrane. In both the absence and presence of PCN, cumulative open time distributions for GABA-activated channels were well fitted by the sum of two exponential terms, characterized by fast (tau f) and slow time constants (tau s). PCN (2mM) reduced the mean value of tau s from 4.29 +/- 0.56 ms (mean +/- s.e. mean) to 1.12 +/- 0.09 ms but had no significant effect on tau f. The mean open time of GABA-activated channels, calculated from the double exponential fits, decreased from 1.39 +/- 0.35 ms to 0.53 +/- 0.02 ms in the presence of 2 mM PCN. The reduced mean open time of GABA-sensitive channels seen in the presence of PCN may contribute to the convulsant action of the drug in vivo.