omega-Toxins affect Na+ currents in neurosecretory insect neurons

omega-toxins specifically block certain Ca2+ channels in mammalian neurons as well as in dorsal unpaired median neurons isolated from the cockroach Periplaneta americana. In these cockroach neurons both the P/Q-type blockers omega-agatoxin IVA and omega-conotoxin MVIIC but not the N-type Ca2+ channel blocker omega-conotoxin GVIA affected fast Na+ currents sensitive to tetrodotoxin and veratridine. Both omega-toxins enhanced Na+ current decay and thus decreased the amplitudes of the peak currents. They also led to a slower recovery from inactivation. Toxin effects developing within a few min were ot removed upon washing. They were not use-dependent. The description of the effect of omega-conotoxin MVIIC on current kinetics in terms of the Hodgkin-Huxley model revealed that steady-state parameters were not affected whereas the time constant of inactivation was considerably reduced. Under control conditions, the inactivation time constant is similar to the time constant of recovery from inactivation. The toxin-induced increase of the latter time constant and the decrease of the inactivation time constant indicate that inactivation can no longer be described by first-order kinetics.