Roles of Kit signalling in smooth muscle tissues

为了阐明Kit（一种受体型酪氨酸激酶）在平滑肌组织自主运动中的作用，我们研究了小鼠胃肠道中Kit阳性（Kit^+）细胞的功能和数量。通过对出生后8天的BALB/c小鼠腹腔注射中和Kit抗体（ACK2），我们发现Kit信号在“Cajal间质细胞（ICCs）”的分化和增殖中起着至关重要的作用，它是胃肠道运动的起心脏和神经调节介质。在用制氨抑素穿孔膜片钳技术的电压箝制条件下，Kit^+-细胞产生节律性Ca^<2+>激活的Cl^-电流。在ack2治疗的小鼠中，胃肠道节律性收缩受损，对缓激肽、乙酰胆碱和前列腺素F_<2a>等药物的收缩反应异常增强。25℃低温脏器浴液的灌注效果可以模拟药物引起的异常收缩，同时伴有节律性收缩受损。综上所述，这表明Kit信号在icc的起搏功能的发展中起着重要作用，并且可能由icc的节律性电输入触发的平滑肌细胞的节律性兴奋放电调节了药物诱导的收缩程度。

To clarify the roles of Kit, a receptor-type tyrosine kinase, in autonomic motility of smooth muscle tissues, we investigated the function and population of Kit-positive (Kit^+) cells in the gastrointestinal tracts of mice. By using of BALB/c mice intraperitoneally injected with neutralizing Kit antibody (ACK2) for 8 days after birth, it was found that Kit signalling plays crucial roles in the differentiation and proliferation of 'interstitial cells of Cajal (ICCs)' as pacemakers and mediators of neural regulation in gastrointestinal motility.Under voltage-clamped conditions with the nystatin-perforated patch-clamp technique, Kit^+-cells developed rhythmic Ca^<2+>-activated Cl^- currents. In the ACK2-treated mice, rhythmic contraction of the gastrointestinal tracts was impaired and the contractile responses to drugs, including bradykinin, acetylcholine and prostaglandin F_<2a>, were anomalously augmented. The anomalous drug-induced contraction, which was accompanied by the impaired rhythmic contraction, was mimicked by the effect of superfusion with a low temperature organ bath solution at 25 ℃. Altogether, it is suggested that Kit signalling plays important roles in development of pacemaking function of ICCs and that rhythmic discharge of excitation of the smooth muscle cells, which may be triggered by rhythmic electrical input from ICCs, regulates the extent of drug-induced contraction.