omega-Conotoxin GVIA and nifedipine inhibit the depolarizing action of the fungal metabolite, destruxin B on muscle from the tobacco budworm (Heliothis virescens).
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; omega-conotoxin GVIA, nifedipine, diltiazem and methoxyverapamil on skeletal muscle from the lepidopteran insect pest, tobacco budworm (Heliothis virescens). At a concentration of 1.7 microM, 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 omega-conotoxin GVIA and nifedipine but not by methoxyverapamil or diltiazem. The inhibitory activity of omega-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 omega-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 omega-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 omega-conotoxin GVIA and nifedipine. The other population is activated by destruxin B and inhibited by omega-conotoxin GIVA and nifedipine.[1]References
- omega-Conotoxin GVIA and nifedipine inhibit the depolarizing action of the fungal metabolite, destruxin B on muscle from the tobacco budworm (Heliothis virescens). Bradfisch, G.A., Harmer, S.L. Toxicon (1990) [Pubmed]
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