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

1 The specific type(s) of voltage-sensitive calcium channels (VSCCs) i nvolved in sympathetic nuerotransmission have not yet been characteriz ed in human vascular tissues. We therefore examined the functional rol e of the N- and L-type VSCCs in human saphenous veins. 2 Contractile r esponse curves for transmural nerve stimulation (TNS) and for exogenou sly administered noradrenaline (NA) were obtained in superfused saphen ous vein rings. The contractions induced by TNS, but not by NA, were i nhibited by 1 muM tetrodotoxin and by 10 muM guanethidine. Both respon ses 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 polyp eptide with specific inhibitory activity on N- and L-type calcium chan nels, the neurally evoked contractions were almost completely abolishe d. In contrast, the responses induced by exogenous NA were not affecte d by the neurotoxin, thus providing evidence of the exclusive presynap tic action of omega-CgTx. 4 In the presence of the calcium antagonist verapamil (10 muM), which selectively blocks L-type VSCCs, the contrac tions induced by both TNS and NA were diminished to the same extent, s uggesting that the organic calcium blocker is active only at the postj unctional level. 5 It is concluded that N-type calcium channels are th e main pathway of calcium entry controlling the functional responses i nduced by activating sympathetic nerves; the role of L-type channels a ppears to be limited to the postjunctional level, modulating smooth mu scle contractions.