Benzodiazepines do not modulate desensitization of recombinant alpha(1)beta(2)gamma(2) GABA(A) receptors

PREVIOUS studies suggest that diazepam (DZP) increases the desensitization rate of GABA(A) receptors, although this effect could simply be a consequen ce of the DZP-induced increase in GABA sensitivity rather than a direct mod ulation of desensitization kinetics. To distinguish these two possibilities , voltage clamp recordings were performed on rat alpha(1)beta(2)gamma(2) GA BA(A) receptors expressed in Xenopus laevis oocytes. Complete GABA concentr ation-response relationships were obtained in the absence and presence of 1 mu M DZP and the observed shift in GABA sensitivity (similar to 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 DZ P on the rate of desensitization is secondary to the increase in GABA sensi tivity and not due to a direct effect on the process of desensitization. Ne uroReport 10:817-821 (C) 1999 Lippincott Williams & Wilkins.