Wegener Jörg W, Schulla Verena, Koller Angela, Klugbauer Norbert, Feil Robert, Hofmann Franz
Institut für Pharmakologie und Toxikologie, Technische Universität München, Biedersteiner Str. 29, München 80802, Germany.
FASEB J. 2006 Jun;20(8):1260-2. doi: 10.1096/fj.05-5292fje. Epub 2006 Apr 24.
The Ca(v)1.2 L-type Ca2+ channel is the dominant voltage-activated Ca2+ channel in heart and smooth muscle. The functional significance of this channel was studied in intestinal smooth muscle from mice carrying a smooth muscle-specific, conditional inactivation of the Ca(v)1.2 gene (Ca(v)1.2SMACKO mice). Inactivation was complete within 4 wk after tamoxifen treatment and confirmed by RT-PCR, Western blot and functional analysis. Ca(v)1.2SMACKO mice show reduced feces excretion, absence of rhythmic contractions in small and large intestinal muscle and signs of paralytic ileus. Extracellular field stimulation evoked smaller contractions in jejunum muscles from Ca(v)1.2SMACKO than from CTR mice, whereas carbachol-induced contractions of similar magnitude in both muscles. The Ca2+ needed for contraction in jejunum was provided mainly by Ca(v)1.2 channels and by store-operated channels in muscles from CTR and Ca(v)1.2SMACKO mice, respectively. In conclusion, the Ca(v)1.2 channel is essential for electromechanical coupling and important for pharmaco-mechanical coupling in intestinal smooth muscle and cannot be substituted functionally by other Ca2+ entry pathways.
Ca(v)1.2 L型钙离子通道是心脏和平滑肌中主要的电压门控钙离子通道。我们利用平滑肌特异性、条件性失活Ca(v)1.2基因的小鼠（Ca(v)1.2SMACKO小鼠），研究了该通道在肠道平滑肌中的功能意义。他莫昔芬处理后4周内失活完成，并通过RT-PCR、蛋白质免疫印迹和功能分析得以证实。Ca(v)1.2SMACKO小鼠粪便排泄减少，小肠和大肠肌肉无节律性收缩，并出现麻痹性肠梗阻迹象。细胞外电场刺激引起Ca(v)1.2SMACKO小鼠空肠肌肉的收缩幅度小于对照小鼠，而卡巴胆碱在两种肌肉中引起的收缩幅度相似。对照小鼠和Ca(v)1.2SMACKO小鼠空肠收缩所需的钙离子分别主要由Ca(v)1.2通道和肌浆网操纵性通道提供。总之，Ca(v)1.2通道对于肠道平滑肌的机电耦联至关重要，对于药理-机械耦联也很重要，并且在功能上不能被其他钙离子内流途径替代。
