Waglerin-1 inhibits GABA(A) current of neurons in the nucleus accumbens ofneonatal rats

The effect of Waglerin-1, a 22-amino acid peptide purified from the venom o f Wagler's pit viper on the whole cell current response (I-GABA) to gamma-a minobutyric acid (GABA) was examined for neurons freshly isolated from the nucleus accumbens of 3- to 7-day-old rats. Waglerin-1 depressed I-GABA indu ced by subsaturating concentrations of GABA; the IC50 for I-GABA induced by 10 mu M GABA was 2.5 mu M Waglerin-1. This concentration of Waglerin-1 shi fted the GABA concentration-response curve to the right in a parallel manne r, increasing the GABA EC50 from 12 +/- 3 to 27 +/- 5 mu M. The depressant effect of Waglerin-1 was greater at negative holding potentials. Zn2+ also inhibited I-GABA with an IC50 of 0.3 mu M. Phosphorylation state appeared t o modulate GABA(A) receptor sensitivity to the inhibitory effect of Wagleri n-1 since dialysis of neurons with N-[2-((p-bromocinnamyl)amino)ethyl]-5-is oquinolinesulfonamide HCl (H-89), an inhibitor of protein kinase A, prevent ed inhibition. The data are discussed in terms of developmental influences on the subunit composition of GABA(A) receptors in neurons of the nucleus a ccumbens. (C) 1999 Elsevier Science B.V. All rights reserved.