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This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/H2723    most recent 00894.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Kiyoshi, H. Articles by Imaizumi, Y. Search for Related Content PubMed PubMed Citation Articles by Kiyoshi, H. Articles by Imaizumi, Y.

Molecular and electrophysiological characteristics of K⁺ conductance sensitive to acidic pH in aortic smooth muscle cells of WKY and SHR

¹Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, Japan; ²Cell Signaling and Ion Channel Research Group, Cellular Pharmacology, School of Pharmacy, Aichigakuin University, Nagoya, Japan; and ³Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Japan

Submitted 20 August 2005 ; accepted in final form 19 June 2006

Changes in K⁺ conductances and their contribution to membrane depolarization in the setting of an acidic pH environment have been studied in myocytes from aortic smooth muscle cells of spontaneously hypertensive rats (SHR) compared with those from Wistar-Kyoto (WKY) rats. The resting membrane potential (RMP) of aortic smooth muscle at extracellular pH (pH_o) of 7.4 was significantly more depolarized in SHR than in WKY rats. Acidification to pH_o 6.5 made this difference in RMP between SHR and WKY rats more significant by further depolarizing the SHR myocytes. Large-conductance Ca²⁺-activated K⁺ (BK) currents, which were markedly suppressed by acidification, were larger in aortic myocytes of SHR than in those of WKY rats. In contrast, acid-sensitive, non-BK currents were smaller in SHR. Western blot analyses showed that expression of BK-- and -₁ subunits in SHR aortas was upregulated and comparable with those in WKY rats, respectively. Additional electrophysiological and molecular studies showed that pH- and halothane-sensitive two-pore domain weakly inward rectifying K⁺ channel (TWIK)-like acid-sensitive K⁺ (TASK) channel subtypes were functionally expressed in aortas, and TASK1 expression was significantly higher in WKY than in SHR. Although the background current through TASK channels at normal pH_o (7.4) was small and may not contribute significantly to the regulation of RMP, TASK channel activation by halothane or alkalization (pH_o 8.0) induced significant hyperpolarization in WKY but not in SHR. In conclusion, the larger depolarization and subsequent abnormal contractions after acidification in aortic myocytes in the setting of SHR hypertension are mainly attributable to the larger contribution of BK current to the total membrane conductance than in WKY aortas.

hypertension; acidic pH-induced contraction; large conductance Ca²⁺-activated K⁺ channel; two-pore domain weakly inward rectifying K⁺ channel-like acid-sensitive K⁺ channel