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

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Abstract
1 The influence of sodium benzylpenicillin (PCN) on membrane channels activated by γ-aminobutyric acid (GABA) was studied in cultured spinal neurones of the mouse by the extracellular patch clamp technique. 2 In whole-cell, current clamp recordings, concentrations of PCN above 0.2 mM significantly reduced the amplitude of the GABA response. 3 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 (τf) and slow time constants (τs). 4 PCN (2 mM) reduced the mean value of τs from 4.29 ± 0.56 ms (mean ± s.e.mean) to 1.12 ± 0.09 ms but had no significant effect on τf. 5 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. 6 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.