Molecular and electrophysiological characteristics of K+ conductance sensitive to acidic pH in aortic smooth muscle cells of WKY and SHR
Molecular and electrophysiological characteristics of K+ conductance sensitive to acidic pH in aortic smooth muscle cells of WKY and SHR
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DOI：
10.1152/ajpheart.00894.2005
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发表时间：
2006-12-01
影响因子：
4.8
通讯作者：
Imaizumi, Yuji
中科院分区：
文献类型：
--
作者：
Kiyoshi, Hidekazu;Yamazaki, Daiju;Imaizumi, Yuji
本文研究了自发性高血压大鼠（SHR）和Wistar-Kyoto（WKY）大鼠主动脉平滑肌细胞在酸性pH环境中K ~+电导的变化及其对膜去极化的影响。在细胞外pH（pHo）为7.4时，SHR主动脉平滑肌静息膜电位（RMP）的去极化程度显著高于WKY大鼠。酸化至pHo 6.5使SHR和WKY大鼠之间的RMP差异更加显著，进一步去极化SHR心肌细胞。SHR主动脉细胞的大电导Ca ~（2+）激活的K ~+（BK）电流明显大于WKY大鼠。与此相反，酸敏感，非BK电流在SHR较小。Western blot分析显示，SHR腹主动脉中BK α和β 1亚基的表达分别上调，与WKY大鼠相当。另外的电生理和分子生物学研究表明，pH和氟烷敏感的双孔结构域弱内向整流K+通道（TWIK）样酸敏感K+通道（ASK）亚型在Alpentas中功能性表达，并且TASK 1在WKY中的表达显著高于SHR。尽管在正常pH值（7.4）下通过ASK通道的背景电流很小，可能对RMP的调节没有显著贡献，但氟烷或碱化（pH（o）8.0）激活的ASK通道在WKY中诱导了显著的超极化，但在SHR中没有。总之，更大的去极化和随后的异常收缩酸化后，在主动脉肌细胞在设置SHR高血压主要是由于BK电流的总膜电导比在WKY动脉粥样硬化的贡献更大。
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 (pHo) of 7.4 was significantly more depolarized in SHR than in WKY rats. Acidification to pHo 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-alpha- and -beta(1) subunits in SHR aortas was upregulated and comparable with those in WKY rats, respectively. Additional electrophysiological and molecular studies showed that pH- and halothanesensitive 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 pHo ( 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.