Involvement of presynaptic voltage-dependent Kv3 channel in endothelin-1-induced inhibition of noradrenaline release from rat gastric sympathetic nerves

Abstract

We previously reported that two types of K+ channels, the BK type Ca2+-activated K+ channel coupled with phospholipase C (PLC) and the voltage-dependent K+ channel (Kv channel), are, respectively, involved in the prostanoid TP receptor- and muscarinic M2 receptor-mediated inhibition of noradrenaline (NA) release from rat gastric sympathetic nerves. In the present study, therefore, we examined whether these K+ channels are involved in endothelin-1-induced inhibition of NA release, using an isolated, vascularly perfused rat stomach. The gastric sympathetic postganglionic nerves around the left gastric artery were electrically stimulated twice at 2.5Hz for 1min, and endothelin-1 was added during the second stimulation. Endothelin-1 (1, 2 and 10nM) dose-dependently inhibited gastric NA release. Endothelin-1 (2nM)-induced inhibition of NA release was neither attenuated by PLC inhibitors [U-73122 (3μM) and ET-18-OCH3 (3μM)] nor by Ca2+-activated K+ channel blockers [charybdotoxin (0.1μM) (a blocker of BK type K+ channel) and apamin (0.3μM) (a blocker of SK type K+ channel)]. The endothelin-1-induced inhibitory response was also not attenuated by α-dendrotoxin (0.1μM) (a selective inhibitor of Kv1 channel), but abolished by 4-aminopyridine (20μM) (a selectively inhibitory dose for Kv3 channel). These results suggest the involvement of a voltage-dependent Kv3 channel in the endothelin-1-induced inhibition of NA release from the gastric sympathetic nerves in rats.