β1-subunit of BK channels regulates arterial wall [Ca2+] and diameter in mouse cerebral arteries
β1-subunit of BK channels regulates arterial wall [Ca2+] and diameter in mouse cerebral arteries
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DOI：
10.1152/jappl.2001.91.3.1350
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发表时间：
2001-09-01
影响因子：
3.3
通讯作者：
Gollasch, M
中科院分区：
文献类型：
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作者：
Löhn, M;Lauterbach, B;Gollasch, M
具有大电导Ca 2+激活的K+（BK）通道基因的破坏的β（1）（BK β（1））亚基的小鼠发展全身性高血压和心脏肥大，这可能是由动脉平滑肌细胞中Ca 2+火花与BK通道解偶联引起的。然而，很少有人知道的生理水平的整体细胞内Ca 2+浓度（[Ca 2 +]（i））和它的调节由Ca 2+火花和BK通道亚基。我们利用BK β（1）基因敲除C57 BL/6小鼠模型，研究了兰尼碱受体和BK通道抑制剂对加压至60 mmHg的脑小动脉整体[Ca 2 +]（i）和直径的影响。Ryanodine（10 μ M）或iberiotoxin（100 nM）增加[Ca 2 +]（i），与75 nM和收缩+/+ BK β（1）野生型动脉相似（加压至60 mmHg）; 10毫米。相比之下，ryanodine（10 mM）或iberiotoxin（100 nM）对[Ca 2 +]（i）和-/- BK β（1）加压（60 mmHg）动脉的直径没有显著影响。这些结果与动脉平滑肌细胞中的Ca 2+火花通过激活BK通道限制肌源性张力的观点一致。Ca ~（2+）火花激活BK通道可通过紧张性超极化降低电压依赖性Ca ~（2+）内流和[Ca ~（2+）]（i）。BK β（1）的缺失破坏了这种负反馈机制，通过增加整体[Ca 2 +]（i）导致动脉张力增加。
Mice with a disrupted beta (1) (BK beta (1))-subunit of the large-conductance Ca2+-activated K+ (BK) channel gene develop systemic hypertension and cardiac hypertrophy, which is likely caused by uncoupling of Ca2+ sparks to BK channels in arterial smooth muscle cells. However, little is known about the physiological levels of global intracellular Ca2+ concentration ([Ca2+](i)) and its regulation by Ca2+ sparks and BK channel subunits. We utilized a BK beta (1) knockout C57BL/6 mouse model and studied the effects of inhibitors of ryanodine receptor and BK channels on the global [Ca2+](i) and diameter of small cerebral arteries pressurized to 60 mmHg. Ryanodine (10 muM) or iberiotoxin (100 nM) increased [Ca2+](i) by similar to 75 nM and constricted +/+ BK beta (1) wildtype arteries (pressurized to 60 mmHg) with myogenic tone by;10 mm. In contrast, ryanodine (10 mM) or iberiotoxin (100 nM) had no significant effect on [Ca2+](i) and diameter of -/- BK beta (1)-pressurized (60 mmHg) arteries. These results are consistent with the idea that Ca2+ sparks in arterial smooth muscle cells limit myogenic tone through activation of BK channels. The activation of BK channels by Ca2+ sparks reduces the voltage-dependent Ca2+ influx and [Ca2+](i) through tonic hyperpolarization. Deletion of BK beta (1) disrupts this negative feedback mechanism, leading to increased arterial tone through an increase in global [Ca2+](i).