Inhibition of a gamma aminobutyric acid A receptor by caffeine.

The effect of caffeine was studied on the progress of gamma aminobutyric acid A receptor channel (GABAAR) mediated transmembrane 36Cl-flux and [3H]GABA release in native membrane vesicles from rat cerebral cortex using rapid kinetic techniques. GABA response on the second time-scale mediated by the slower desensitizing GABAAR was inactivated by 5 mM caffeine whereas subsecond GABA response retained activity. An inhibitor of caffeine-evoked GABA release, dantrolene (0.025 mM), inhibited the effect of caffeine on GABA-mediated transmembrane 36Cl- ion flux. The caffeine-evoked GABA release indicated a rise of [Ca2+]i near to completion within 0.2 s. It can be assumed that elevated [Ca2+]i during depolarization and inhibition of GABAAR with longer mean lifetime function together resulting in a disinhibition of neurotransmission.