Ginkgolide B preferentially blocks chloride channels formed by heteromeric glycine receptors in hippocampal pyramidal neurons of rat

It has been found recently that the platelet activating factor antagonist ginkgolide B is a selective use-dependent blocker of glycine-gated chloride channels. GABA(A) receptor antagonist picrotoxin is known to block alpha homomeric glycine (Gly) receptors, being less effective for heteromeric alpha1/beta glycine receptors. Studying pyramidal hippocampal neurons of rat, we have confirmed that the effect of picrotoxin depends on the age of the animals. Its blocking ability was characterised by IC50 = 140 +/- 12 muM and IC50 = 354 +/- 43 muM for 7 and 14 days old rats, respectively, indicating at a possibly increased contribution of heteromeric receptors with animals age. We have revealed that the blocking action of ginkgolide B is subjected to a more drastic change in the same range of ages: the IC50 value is decreased from 1.6 +/- 0.2 muM for 7days old rats to 0.27 +/- 0.01 muM for 14 days old rats. When measured on the background of ginkgolide B (1 muM), IC50 for picrotoxin was 92 +/- 16 muM. Taken together, these findings indicate that ginkgolide B has higher affinity to heteromeric Gly receptor-gated channels than to the homomeric ones. (C) 2004 Elsevier Inc. All rights reserved.