Differential effects of voltage-dependent Ca2+ channels on low and high frequency mediated neurotransmission in guinea-pig ileum and rat vas deferens
Abstract
The omega-conotoxins GVIA, MVIIA, MVIIC and SVIB reduced in a concentration-dependent manner the low frequency electrically stimulated twitch response of the guinea-pig ileum and rat vas deferens. The relative activities of the conotoxins showed some difference between the two preparations in that for ileum it was MVIIA = GVIA > MVIIC = SVIB and for the vas deferens it was MVIIA > GVIA >> SVIB > MVIIC. High frequency electrical stimulation of both preparations resulted in a neurally-mediated omega-conotoxin GVIA resistant component that was sensitive to high concentrations of either omega-conotoxin MVIIC (300 nM- 1 microM) or omega-agatoxin IVA (300 nM-1 microM) but not to omega-conotoxin MVIIA. Lower levels of either omega-conotoxin MVIIC or omega-agatoxin IVA (30-100 nM) failed to significantly affect the omega-conotoxin GVIA resistant component. This omega-conotoxin GVIA resistant component was large in the ileal preparation comprising 30-40% of the maximal response at 20 Hz but relatively small (10%) in the vas deferens. These studies revealed that the N-type voltage-dependent calcium channel (VDCCs) exclusively controls neurotransmission during low frequency stimulation but at higher frequencies there is an additional non-adrenergic, non-cholinergic (NANC) neurotransmission that appears to be regulated via Q-type VDCC.
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