Penicillin blocks human α 1β 1 and α 1β 1γ 2S GABA A channels that open spontaneously

Abstract

We used the open-channel blocker, penicillin (10 mM), as a tool to investigate if the human α 1β 1 or α 1β 1γ 2S γ-aminobutyric acid type A (GABA A) receptor channels opened in the absence of GABA. Application of penicillin to cells expressing the receptors resulted in a transient inward whole-cell current, the off-current, upon penicillin removal. The amplitude of the off-current was dependent on the duration of the penicillin application, it reversed in polarity at depolarized potentials and exhibited “run-down” similar to the GABA-activated currents. Bicuculline (100 μM) blocked the off-current response. Pentobarbital (50 μM) enhanced the peak off-current amplitude by 2.8 and 3.4 in α 1β 1 and α 1β 1γ 2S receptors, respectively. Diazepam (1 μM) only enhanced the off-current peak response in α 1β 1γ 2S receptors (1.6) and induced the development of an inward current when applied alone. The results are consistent with that the α 1β 1 or α 1β 1γ 2S GABA A receptors can open in the absence of GABA and raise the question of what role spontaneous channel openings have in the function of GABA A receptors.