Submitted on August 20, 2005
Accepted on June 19, 2006
Molecular and electrophysiological characteristics of K+conductance sensitive to acidic pH in aortic smooth muscle cells of WKY and SHR
Hidekazu Kiyoshi1, Daiju Yamazaki1, Susumu Ohya1, Mika Kitsukawa1, Katsuhiko Muraki2, Shin-ya Saito3, Yasushi Ohizumi3, and Yuji Imaizumi1*
1 Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan
2 Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan; Cellular Pharmacology, School of Pharmacy, Aichigakuin University, Nagoya, Aichi, Japan
3 Pharmaceutical Molecular Biology, Graduate School pf Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan
* To whom correspondence should be addressed. E-mail: yimaizum{at}phar.nagoya-cu.ac.jp.
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) in comparison with those from Wistar-Kyoto rats (WKY). The resting membrane potential (RMP) of aortic smooth muscle at extracellular pH (pHo) of 7.4 was significantly more depolarized in SHR than in WKY. Acidification to pHo6.5 made this difference in RMP between SHR and WKY 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. 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 up-regulated and comparable to those in WKY, respectively. Additional electrophysiological and molecular studies showed that pH- and halothane-sensitive 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 pHo (7.4) was small and may not contribute significantly to the regulation of RMP, TASK channel activation by halothane or alkalization (pHo 8.0) induced significant hyperpolarization in WKY but not in SHR. In conclusion, the larger depolarization and subsequent abnormal contractions following acidification in aortic myocytes in the setting of SHR hypertension are mainly attributable to larger contribution of BK current to total membrane conductance than in WKY aortas.
