Waglerin-1 inhibits GABAA current of neurons in the nucleus accumbens of neonatal rats

The effect of Waglerin-1, a 22-amino acid peptide purified from the venom of Wagler's pit viper on the whole cell current response (I-GABA) to gamma-aminobutyric acid (GABA) was examined for neurons freshly isolated from the nucleus accumbens of 3- to 7-day-old rats. Waglerin-1 depressed I-GABA induced 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 shifted the GABA concentration-response curve to the right in a parallel manner, 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 to modulate GABA(A) receptor sensitivity to the inhibitory effect of Waglerin-1 since dialysis of neurons with N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide HCl (H-89), an inhibitor of protein kinase A, prevented inhibition. The data are discussed in terms of developmental influences on the subunit composition of GABA(A) receptors in neurons of the nucleus accumbens. (C) 1999 Elsevier Science B.V. All rights reserved.