Mice with disrupted BK channel β1 subunit gene feature abnormal Ca2+ spark/STOC coupling and elevated blood pressure
Mice with disrupted BK channel β1 subunit gene feature abnormal Ca2+ spark/STOC coupling and elevated blood pressure
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DOI：
10.1161/01.res.87.11.e53
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发表时间：
2000-11-24
影响因子：
20.1
通讯作者：
Pongs, O
中科院分区：
文献类型：
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作者：
Plüger, S;Faulhaber, J;Pongs, O
血管平滑肌细胞 (VSMC) 中的大电导钾 (BK) 通道可感知膜电位和细胞内 Ca2+ 浓度的变化。 BK 通道可通过将膜去极化和细胞内 Ca2+ 浓度（Ca2+ 火花）的局部增加与自发瞬态外向 KC 电流（STOC）复极化联系起来，作为血管张力的负反馈调节器。 BK 通道由通道形成 BK α 和辅助 BK β1 亚基组成，这使 BK 通道对膜电位和 Ca2+ 的变化具有更高的敏感性。为了评估该 β 亚基的体内功能，生成了 BK β1 基因被破坏的小鼠。 BK beta1 -/- 小鼠的脑动脉 VSMC 产生正常幅度和频率的 Ca2+ 火花，但 STOC 频率在生理膜电位下大幅降低。我们的结果表明，BK beta1 -/- 小鼠具有异常的 Ca2+ 火花/STOC 耦合，该耦合转变为更去极化的电位。 BK beta1 -/- 小鼠的胸主动脉环对激动剂和升高的 KCl 做出反应，收缩力增加。 BK beta1 -/- 小鼠的全身血压高于 BK beta1 +/+ 小鼠，但对 α (1)-肾上腺素能血管收缩和一氧化氮介导的血管舒张反应正常。我们认为 BK beta1 -/- 小鼠血压升高有助于使 Ca2+ Spark/STOC 耦合正常化，从而调节肌源性张力。本文全文可在 http://www.circresaha.org 上获取。
Large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) sense both changes in membrane potential and in intracellular Ca2+ concentration. BK channels may serve as negative feedback regulators of vascular tone by linking membrane depolarization and local increases in intracellular Ca2+ concentration (Ca2+ sparks) to repolarizing spontaneous transient outward KC currents (STOCs). BK channels are composed of channel-forming BK alpha and auxiliary BK beta1 subunits, which confer to BK channels an increased sensitivity for changes in membrane potential and Ca2+. To assess the in vivo functions of this beta subunit, mice with a disrupted BK beta1 gene were generated. Cerebral artery VSMCs from BK beta1 -/- mice generated Ca2+ sparks of normal amplitude and frequency, but STOC frequencies were largely reduced at physiological membrane potentials. Our results indicate that BK beta1 -/- mice have an abnormal Ca2+ spark/STOC coupling that is shifted to more depolarized potentials. Thoracic aortic rings from BK beta1 -/- mice responded to agonist and elevated KCl with an increased contractility. BK beta1 -/- mice had higher systemic blood pressure than BK beta1 +/+ mice but responded normally to alpha (1)-adrenergic vasoconstriction and nitric oxide-mediated vasodilation. We propose that the elevated blood pressure in BK beta1 -/- mice serves to normalize Ca2+ spark/STOC coupling for regulating myogenic tone. The full text of this article is available at http://www.circresaha.org.