OMEGA-CONOTOXIN GVIA AND NIFEDIPINE INHIBIT THE DEPOLARIZING ACTION OF THE FUNGAL METABOLITE, DESTRUXIN-B ON MUSCLE FROM THE TOBACCO BUDWORM (HELIOTHIS-VIRESCENS)

G. A. Bradfisch and S. L. Harmer. ω-Conotoxin GVIA and nifedipine inhibit the depolarizing action of the fungal metabolite, destruxin B on muscle from the tobacco budworm (Heliothis virescens). Toxicon 28, 1249-1254, 1990.-Recent studies on a group of fungal metabolites, collectively called the destruxins, have suggested that these compounds activate calcium influx in insect skeletal muscle. In this study, we have investigated the sensitivity of destruxin B to the voltage-dependent calcium channel antagonists; ω-conotoxin GVIA, nifedipine, diltiazem and methoxyverapamil on skeletal muscle from the lepidopteran insect pest, tobacco budworm (Heliothis virescens). At a concentration of 1.7 μM, destruxin B caused a rapid decrease in the transmembrane resting potential. The effect of destruxin B on insect muscle was blocked by micromolar concentrations of ω-conotoxin GVIA and nifedipine but not by methoxyverapamil or diltiazem. The inhibitory activity of ω-conotoxin GVIA on invertebrate muscle tissue was surprising since this compound was previously thought to be selective to vertebrate nervous tissue. The sensitivity of the destruxin-stimulated depolarization to the two antagonists suggested that destruxin B activated a voltage-dependent calcium channel. Neuromuscular transmission was monitored in the presence of ω-conotoxin GVIA and nifedipine to investigate the physiological role of the destruxin-activated channel. Neither antagonist altered the waveform of graded action potentials produced by synaptic activation. The lack of effect of ω-conotoxin GVIA and a high dose of nifedipine could be explained by the existence of two populations of pharmacologically distinct voltage-dependent calcium channels on the muscle membrane. One population which is involved with the production of graded action potentials is insensitive to ω-conotoxin GVIA and nifedipine. The other population is activated by destruxin B and inhibited by ω-conotoxin GVIA and nifedipine. © 1990.