EVIDENCE FOR SYMPATHETIC NEUROTRANSMISSION THROUGH PRESYNAPTIC N-TYPE CALCIUM CHANNELS IN HUMAN SAPHENOUS-VEIN

1 The specific type(s) of voltage-sensitive calcium channels (VSCCs) involved in sympathetic nuerotransmission have not yet been characterized in human vascular tissues. We therefore examined the functional role of the N- and L-type VSCCs in human saphenous veins. 2 Contractile response curves for transmural nerve stimulation (TNS) and for exogenously administered noradrenaline (NA) were obtained in superfused saphenous vein rings. The contractions induced by TNS, but not by NA, were inhibited by 1 muM tetrodotoxin and by 10 muM guanethidine. Both responses were substantially reduced by 1 muM phentolamine, indicating that the contractions evoked by TNS were mediated by endogenous NA released from noradrenergic nerves. 3 In the presence of 2 muM omega-conotoxin GVIA (omega Contus Geographus toxin, fraction VI A; co-CgTx), a polypeptide with specific inhibitory activity on N- and L-type calcium channels, the neurally evoked contractions were almost completely abolished. In contrast, the responses induced by exogenous NA were not affected by the neurotoxin, thus providing evidence of the exclusive presynaptic action of omega-CgTx. 4 In the presence of the calcium antagonist verapamil (10 muM), which selectively blocks L-type VSCCs, the contractions induced by both TNS and NA were diminished to the same extent, suggesting that the organic calcium blocker is active only at the postjunctional level. 5 It is concluded that N-type calcium channels are the main pathway of calcium entry controlling the functional responses induced by activating sympathetic nerves; the role of L-type channels appears to be limited to the postjunctional level, modulating smooth muscle contractions.