Benzodiazepines do not modulate desensitization of recombinant alpha1beta2gamma2 GABA(A) receptors.
Previous studies suggest that diazepam (DZP) increases the desensitization rate of GABA(A) receptors, although this effect could simply be a consequence of the DZP-induced increase in GABA sensitivity rather than a direct modulation of desensitization kinetics. To distinguish these two possibilities, voltage clamp recordings were performed on rat alpha1beta2gamma2 GABA(A) receptors expressed in Xenopus laevis oocytes. Complete GABA concentration-response relationships were obtained in the absence and presence of 1 microM DZP and the observed shift in GABA sensitivity (approximately 2.5-fold) was used to adjust GABA and GABA plus DZP to the same level of activation. In this case, DZP had no significant effect on either the rate of onset or recovery from desensitization. This suggests that the apparent effect of DZP on the rate of desensitization is secondary to the increase in GABA sensitivity and not due to a direct effect on the process of desensitization.
Ghansah
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Department of Neurobiology, The University of Alabama at Birmingham, School of Medicine, 35294-0021, USA.
Weiss
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DS
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D007700:Kinetics; D018408:Patch-Clamp Techniques; D051381:Rats; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000187:drug effects*; D014158:Transcription, Genetic; D014982:Xenopus laevis
D018118:Chloride Channels; D018757:GABA Modulators; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D003975:Diazepam