Relationship between ATP-sensitive potassium channel and the phosphorylation of ERK1/2 in human pulmonary arterial smooth muscle cells

Objective To study the relationship between ATP-sensitive potassium channel and the phosphorylation of extracellular signal regulated kinase 1/2(ERK1/2) in human pulmonary arterial smooth muscle cells. Methods By Western-blot analysis,the phosphorylation levels of ERK1/2 were measured in primary cultured human pulmonary arterial smooth muscle cells.Except for no intervention for control group,other groups were incubated with endothelin-1(ET-1),ET-1 + iptakalim,pinacidil or glibenclamide. Results ①ET-1 induced phosphorylation of ERK1/2 from 2 to 30 min with a peak response observed at 10 min in a time-dependent manner.②Iptakalim and pinacidil inhibited ET-1-induced ERK1/2 phosphorylation.③Glibenclamide,a selective KATP channel antagonist,could antagonize the effects of iptakalim and pinacidil. Conclusions KATP channel openers inhibited ET-1-induced phosphorylation of ERK1/2 in primary cultured human pulmonary arterial smooth muscle cells probably through activating KATP channel and KATP channel will be most promising target for new drugs to treat pulmonary arterial hypertension.