Waglerin-1 inhibits GABA(A) 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 IC(50) for I(GABA) induced by 10 microM GABA was 2.5 microM Waglerin-1. This concentration of Waglerin-1 shifted the GABA concentration-response curve to the right in a parallel manner, increasing the GABA EC(50) from 12+/-3 to 27+/-5 microM. The depressant effect of Waglerin-1 was greater at negative holding potentials. Zn(2+) also inhibited I(GABA) with an IC(50) of 0.3 microM. 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.