Szigeti Gyula Péter, Szappanos Henrietta, Deli Tamás, Cseri Julianna, Kovács László, Csernoch László
Department of Physiology, Medical and Health Science Centre, University of Debrecen, P.O. Box 22, 98 Nagyerdei krt., Debrecen, 4012, Hungary.
Pflugers Arch. 2007 Jan;453(4):509-18. doi: 10.1007/s00424-006-0145-7. Epub 2006 Sep 26.
Although extracellular adenosine triphosphate (ATP) has been generally accepted as the regulator of cellular differentiation, the relative contribution of the various purinoreceptor subtypes to purinergic signalling at distinct stages of skeletal muscle differentiation is still poorly understood. Here we measured extracellular ATP-evoked changes in intracellular calcium concentration and surface membrane ionic currents (I (ATP)), calculated the calcium flux (FL) entering the myoplasmic space and compared these parameters at different stages of differentiation on cultured mouse myotubes. The ATP-evoked FL displayed an early peak and then declined to a steady level. With differentiation, the early peak became separated from the maintained component and was absent on mature myotubes. Repeated ATP applications caused desensitization of the response in both immature and differentiated myotubes, owing mainly to the reduction of the early peak of FL in the former and to a decline of both components in the latter group of cells. Depolarization of the cell or removal of external calcium suppressed the early peak. I (ATP) showed no inactivation, and its voltage dependence displayed strong inward rectification. The concentration dependence of I (ATP) can be fitted using a Hill equation, yielding an EC(50) of 56 microM. Results are consistent with the parallel activation of both P2X and P2Y receptors.
尽管细胞外三磷酸腺苷（ATP）已被普遍认为是细胞分化的调节因子，但在骨骼肌分化的不同阶段，各种嘌呤受体亚型对嘌呤能信号传导的相对贡献仍知之甚少。在这里，我们测量了细胞外ATP引起的细胞内钙浓度和表面膜离子电流（I(ATP)）的变化，计算了进入肌浆空间的钙通量（FL），并在培养的小鼠肌管分化的不同阶段比较了这些参数。ATP引起的FL显示出一个早期峰值，然后下降到一个稳定水平。随着分化的进行，早期峰值与维持成分分离，在成熟肌管上不存在。重复施加ATP导致未成熟和分化肌管中的反应脱敏，主要是由于前者中FL早期峰值的降低以及后者细胞中两个成分的下降。细胞去极化或去除细胞外钙会抑制早期峰值。I(ATP)没有失活，其电压依赖性表现出强烈的内向整流。I(ATP)的浓度依赖性可以用希尔方程拟合，得出的EC50为56微摩尔。结果与P2X和P2Y受体的平行激活一致。
