Human myofibroblastic hepatic stellate cells express Ca2+-activated K+ channels that modulate the effects of endothelin-1 and nitric oxide

Background/Aims: High-conductance Ca2+-activated K+ (BKCa) channels modulate the effects of vasoactive factors in contractile cells. It is unknown whether hepatic stellate cells (HSCs) contain BKCa channels and what their role in the regulation of HSCs contractility is. Methods: The presence of BKCa channels in HSCs was assessed by the patch-clamp technique. The functional role of BKCa channels was investigated by measuring intracellular calcium concentration ([Ca2+]i) and cell contraction in individual cells after stimulation with endothelin-1 in the presence or absence of specific modulators of BKCa channels. Results: BKCa channels were detected by patch-clamp in most of the activated HSCs studied. Incubation of cells with iberiotoxin, a BKCa channel blocker, increased both the sustained phase of [Ca2+]i elicited by endothelin-1 and the number of cells undergoing contraction, while the use of NS1619, a BKCa channel opener, induced opposite effects. Stimulation of HSCs with S-nitroso-N-acetyl-penicillamine (SNAP), a nitric oxide (NO)-donor, increased the opening of BKCa channels and reduced the effects of endothelin-1. Conversely, iberiotoxin abolished the inhibitory effect of SNAP on endothelin-induced [Ca2+]i increase and cell contraction. Conclusions: Activated human HSCs contain BKCa channels that modulate the contractile effect of endothelin-1 and mediate the inhibitory action of NO.