Elsevier

Brain Research

Volume 442, Issue 2, 1 March 1988, Pages 287-296
Brain Research

Research report
Quantitative evaluation of the properties of a pyridazinyl GABA derivative (SR 95531) as a GABAA competitive antaginist. An electrophysiological approach

https://doi.org/10.1016/0006-8993(88)91514-4Get rights and content

Abstract

We have investigated the effects of an aryl-aminopyridazine derivative of GABA (SR 95531) on dose-response curves of GABA-induced depolarizations from dorsal root ganglion neurones recorded intracellularly. The reversible shift to the right of the dose-response curves in a parallel fashion and the dissociation constant (KB value of 0.13 ± 0.02 μM (n = 15) indicate that this compound is a potent competitive GABAA antagonist. The competitive nature of SR 95531-induced antagonism was confirmed by single channel analysis. In excised membrane patches from bovine chromaffin cells (outside out configuration), 0.2–0.5 μM SR 95531 did not alter the mean open time of GABA-activated channels and did not introduce further short closing gaps within bursts. Whole cell recordings from cultured nodose ganglion neurones indicated that SR 95531 (10μM) did not modify significantly any of the 3 types of calcium currents already reported in sensory neurones. This result might be of importance for further studies of presynaptic GABA actions on transmitter release.

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