Semenov Iurii, Wang Bin, Herlihy Jeremiah T, Brenner Robert
Department of Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA.
Am J Physiol Lung Cell Mol Physiol. 2006 Oct;291(4):L802-10. doi: 10.1152/ajplung.00104.2006. Epub 2006 Apr 21.
The large-conductance, Ca2+-activated K+ (BK) channels are regulators of voltage-dependent Ca2+ entry in many cell types. The BK channel accessory beta1-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 beta1-subunit has not been investigated. Utilizing the gene-targeted mice for the beta1-subunit gene, we have investigated the role of the beta1-subunit in tracheal smooth muscle. In mice with the beta1-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 beta1-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 beta1-subunit and BK channel block with paxillin, indicating that BK channels contribute little to airway relaxation in the absence of the beta1-subunit. Utilizing nifedipine, we found that the increased constriction caused by knockout of the beta1-subunit could be accounted for by an increased recruitment of L-type voltage-dependent Ca2+ channels. These results indicate that the beta1-subunit is required in airway smooth muscle for control of voltage-dependent Ca2+ influx during rest and after cholinergic signaling in BK channels.
大电导钙激活钾（BK）通道是多种细胞类型中电压依赖性钙内流的调节因子。BK通道辅助β1亚基可促进平滑肌中的通道激活，是血管系统和膀胱正常张力所必需的。然而，尽管BK通道也与气道平滑肌功能有关，但其受β1亚基的调节尚未得到研究。利用β1亚基基因的基因靶向小鼠，我们研究了β1亚基在气管平滑肌中的作用。在具有β1亚基敲除等位基因的小鼠中，切除的气管平滑肌片中BK通道活性显著降低，全气管平滑肌细胞中的自发性BK电流减少。β1亚基的敲除导致静息钙水平升高以及胆碱能信号传递后钙内流的持续成分增加。气管收缩研究表明，β1亚基敲除和用帕西利宁阻断BK通道后的收缩水平相同，这表明在没有β1亚基的情况下，BK通道对气道舒张的作用很小。利用硝苯地平，我们发现β1亚基敲除引起的收缩增加可由L型电压依赖性钙通道募集增加来解释。这些结果表明，气道平滑肌中BK通道在静息时以及胆碱能信号传递后控制电压依赖性钙内流需要β1亚基。
