BK channel β1-subunit regulation of calcium handling and constriction in tracheal smooth muscle
BK channel β1-subunit regulation of calcium handling and constriction in tracheal smooth muscle
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DOI：
10.1152/ajplung.00104.2006
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发表时间：
2006-10-01
影响因子：
4.9
通讯作者：
Brenner, Robert
中科院分区：
文献类型：
--
作者：
Semenov, Iurii;Wang, Bin;Brenner, Robert
BK通道β（1）-亚单位对气管平滑肌钙处理和收缩的调节。美国生理学杂志肺细胞分子生理学291：L 802-L 810，2006年。首次出版于2006年4月21日; doi：10.1152/ajplung。00104.2006.-在许多细胞类型中，大电导、Ca 2+激活的K+（BK）通道是电压依赖性Ca 2+内流的调节剂。BK通道辅助β 1亚基促进平滑肌中的通道激活，并且是脉管系统和膀胱中的适当张力所需的。然而，尽管BK通道也与气道平滑肌功能有关，但尚未研究β（1）亚基对它们的调节。利用β 1亚基基因的基因靶向小鼠，我们研究了β 1亚基在气管平滑肌中的作用。在β（1）-亚基敲除等位基因的小鼠中，离体气管平滑肌斑的BK通道活性显著降低，整个气管平滑肌细胞的自发BK电流降低。β（1）-亚基的敲除导致静息Ca 2+水平的增加和胆碱能信号传导后Ca 2+内流的持续成分的增加。气管收缩研究表明，收缩水平与敲除β（1）-亚基和用桩蛋白阻断BK通道相同，表明在β（1）-亚基不存在的情况下，BK通道对气道舒张的贡献很小。利用硝苯地平，我们发现敲除β（1）亚基引起的收缩增加可以通过增加L型电压依赖性Ca 2+通道的募集来解释。这些结果表明，β（1）-亚单位是需要在气道平滑肌控制电压依赖性的Ca 2+内流在休息期间和后BK通道的胆碱能信号。
BK channel beta(1)-subunit regulation of calcium handling and constriction in tracheal smooth muscle. Am J Physiol Lung Cell Mol Physiol 291: L802-L810, 2006. First published April 21, 2006; doi:10.1152/ajplung. 00104.2006.-The large-conductance, Ca2+-activated K+ (BK) channels are regulators of voltage-dependent Ca2+ entry in many cell types. The BK channel accessory beta 1-subunit promotes channel activation in smooth muscle and is required for proper tone in the vasculature and bladder. However, although BK channels have also been implicated in airway smooth muscle function, their regulation by the beta(1)-subunit has not been investigated. Utilizing the gene-targeted mice for the beta(1)-subunit gene, we have investigated the role of the beta(1)-subunit in tracheal smooth muscle. In mice with the beta(1)-subunit-knockout allele, BK channel activity was significantly reduced in excised tracheal smooth muscle patches and spontaneous BK currents were reduced in whole tracheal smooth muscle cells. Knockout of the beta(1)-subunit resulted in an increase in resting Ca2+ levels and an increase in the sustained component of Ca2+ influx after cholinergic signaling. Tracheal constriction studies demonstrate that the level of constriction is the same with knockout of the beta(1)-subunit and BK channel block with paxillin, indicating that BK channels contribute little to airway relaxation in the absence of the beta(1)-subunit. Utilizing nifedipine, we found that the increased constriction caused by knockout of the beta(1)-subunit could be accounted for by an increased recruitment of L-type voltage-dependent Ca2+ channels. These results indicate that the beta(1)-subunit is required in airway smooth muscle for control of voltage-dependent Ca2+ influx during rest and after cholinergic signaling in BK channels.