title: Epithelial Na+ channel proteins are mechanotransducers of myogenic constriction in rat posterior cerebral arteries.
abstract: It has been suggested that mechanosensitive ion channels initiate myogenic responses in vessels; however, the molecular identity of the mechanosensitive ion channel complex is unknown. Although previous reports have suggested that epithelial Na(+) channel (ENaC) proteins are mechanotransducers in arteries, experimental evidence demonstrating that ENaC proteins are mechanotransducers are not fully elucidated. The goal of the present study was to determine whether the ENaC is a mechanotransducer for the myogenic response by providing supporting evidence in the rat posterior cerebral artery (PCA). We measured the effect of ENaC inhibition on the pressure-induced myogenic response, Ca(2+) concentration and 20 kDa myosin light chain (MLC(20)) phosphorylation. We detected expression of βENaC and γENaC subunits in rat PCA by Western blots and immunofluorescence. Inhibition of ENaCs with amiloride, ethyl isopropyl amiloride or benzamil blocked the myogenic response. Moreover, the myogenic response was inhibited in rat PCA transfected with βENaC and γENaC small interfering RNA. The myogenic response was inhibited by elimination of external Na(+), which was replaced with N-methyl-d-glucamine. Amiloride and nifedipine inhibited the pressure-induced increase in Ca(2+) concentration. Finally, MLC(20) increased when the intraluminal pressure was raised, and the pressure-induced increase in MLC(20) phosphorylation was inhibited by pretreatment with amiloride, and in arteries transfected with βENaC or γENaC small interfering RNA. Our results suggest that ENaCs may play an important role as mechanosensitive ion channels initiating pressure-induced myogenic responses in rat PCA.
authors.affiliation: Department of Physiology, College of Medicine, BK 21 Project for Medical Sciences, Yonsei University, CPO Box 8044, Seoul, 120-752, Korea
authors.forename: Eok-Cheon
authors.initials: EC
authors.lastname: Kim
authors.forename: Duck-Sun
authors.initials: DS
authors.lastname: Ahn
authors.forename: Soo-In
authors.initials: SI
authors.lastname: Yeon
authors.forename: Mihwa
authors.initials: M
authors.lastname: Lim
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
mesh_terms: D000818:Animals; D053503:Epithelial Sodium Channels / Q000502:physiology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D020769:Posterior Cerebral Artery / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D053503:Epithelial Sodium Channels; D034741:RNA, Small Interfering; C507050:Scnn1b protein, rat; C507054:Scnn1g protein, rat