BK通道广泛的分布于各类肌细胞质膜,调控细胞的收缩与舒张。在成年哺乳动物心肌细胞，BK通道主要分布于线粒体内膜。胚胎期BK通道分布于心肌细胞膜而成熟时分布在线粒体的机制以及BK通道在成年心肌细胞收缩与舒张过程中是否发挥作用，这些问题都不清楚。本研究应用BK通道基因敲除小鼠，通过膜片钳记录、钙成像和牵引力显微镜技术，分析BK通道基因敲除后对心肌细胞收缩力、静息电位、动作电位、自发性钙震荡的影响。并通过免疫组化，BK通道与L-型钙通道（心肌细胞主要表达的钙通道）共表达结合阻断肌质网ryanodine 受体确定BK通道调控心肌细胞功能的机制。本项目还分别在不同刚度和化学成分的细胞外基质上培养心肌细胞，确定力学因素还是化学因素为决定BK通道在成年心肌细胞主要定位于线粒体内膜的原因。这些研究为认识和治疗与心脏发育相关的疾病以及心肌纤维化、心肌肥大等疾病的发病机制提供重要的参考。

The large conductance Ca2+ sensitive K+ (BK) channel is widely expressed in plasma membrane of various kinds of muscle cells, generally functioning to regulate cell contraction and relaxation. Previous studies suggested that the BK channel is mainly distributed in the plasma membrane of embryonic carcardiomyocyts but highly expressed in the mitochondrial inner membrane in matured cadiomyocytes. Whether the BK channel can regulate the contraction or relaxation of the matured myocardial cells remains elusive. In present study, we used the BK gene knock-out mice to investigate the influence of the BK channel on the function of cardiomyocytes, including the resting potential, the action potential, the spontaneous calcium oscillation and the contraction force. Using immunofluorescence and patch-clamp recording technology combine block the Ryandine receptor to determine the mechanism of BK channel regulating the function of cardimyocytes. Furthermore, the cardiomyocytes were cultured on substrates with different stiffness or different chemical component respectively, to clarify mechanism regulating BK channel locate in the sarcoplasmic reticulum of matured myocardial cells rather than in the plasma membrane. Such information is useful for understanding the mechanism of various cardiac diseases, such as developmental heart diseases, myocardial fibrosis and myocardial hypertrophy, etc.