Penicillin blocks human alpha 1 beta 1 and alpha 1 beta 1 gamma 2S GABAA channels that open spontaneously.
We used the open-channel blocker, penicillin (10 mM), as a tool to investigate if the human alpha1beta1 or alpha1beta1gamma2S gamma-aminobutyric acid type A (GABAA) 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 microM) blocked the off-current response. Pentobarbital (50 microM) enhanced the peak off-current amplitude by 2.8 and 3.4 in alpha1beta1 and alpha1beta1gamma2S receptors, respectively. Diazepam (1 microM) only enhanced the off-current peak response in alpha1beta1gamma2S receptors (1.6) and induced the development of an inward current when applied alone. The results are consistent with that the alpha1beta1 or alpha1beta1gamma2) GABAA receptors can open in the absence of GABA and raise the question of what role spontaneous channel openings have in the function of GABAA receptors.
Molecular and Cellular Physiology, Department of Physiological Sciences, Lund University, Tornavagen 10 BMC F11, 22184 Lund, Sweden.
Catarina E L
CE
Lindquist
Julie E
JE
Dalziel
Brett A
BA
Cromer
Bryndis
B
Birnir
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006801:Humans; D010406:Penicillins / Q000494:pharmacology*; D021122:Protein Subunits / Q000037:antagonists & inhibitors* / Q000145:classification / Q000502:physiology; D051381:Rats; D011963:Receptors, GABA-A / Q000145:classification / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; C546240:GABRA1 protein, human; C546279:GABRG2 protein, human; D010406:Penicillins; D021122:Protein Subunits; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid