Human myofibroblastic hepatic stellate cells express Ca 2+-activated K + channels that modulate the effects of endothelin-1 and nitric oxide

Abstract

Background/Aims : High-conductance Ca 2+-activated K + (BK Ca) channels modulate the effects of vasoactive factors in contractile cells. It is unknown whether hepatic stellate cells (HSCs) contain BK Ca channels and what their role in the regulation of HSCs contractility is. Methods : The presence of BK Ca channels in HSCs was assessed by the patch-clamp technique. The functional role of BK Ca channels was investigated by measuring intracellular calcium concentration ([Ca 2+] i) and cell contraction in individual cells after stimulation with endothelin-1 in the presence or absence of specific modulators of BK Ca channels. Results : BK Ca channels were detected by patch-clamp in most of the activated HSCs studied. Incubation of cells with iberiotoxin, a BK Ca channel blocker, increased both the sustained phase of [Ca 2+] i elicited by endothelin-1 and the number of cells undergoing contraction, while the use of NS1619, a BK Ca channel opener, induced opposite effects. Stimulation of HSCs with S-nitroso- N-acetyl-penicillamine (SNAP), a nitric oxide (NO)-donor, increased the opening of BK Ca channels and reduced the effects of endothelin-1. Conversely, iberiotoxin abolished the inhibitory effect of SNAP on endothelin-induced [Ca 2+] i increase and cell contraction. Conclusions : Activated human HSCs contain BK Ca channels that modulate the contractile effect of endothelin-1 and mediate the inhibitory action of NO.