Studies on the molecular mechanism of calcium signaling and the role of IP3 receptor in development and differentiation

肌醇1,4,5-三磷酸（IP3）受体（IP3R）在内部Ca2+储存中作为Ca2+释放通道。1型IP3R（IP3R1）富集于鸡背根神经节神经元生长锥中。内部Ca2+储存的消耗和药物抑制IP3信号传导抑制了神经突的延伸。微量注射肝素，一种竞争性IP3R阻滞剂，诱导神经突缩回。发色团辅助激光失活诱导生长锥IP3R1急性局部功能丧失，导致生长锥停滞和神经突缩回。ip3诱导的生长锥中Ca2+释放似乎在控制神经生长中起关键作用。[Ca2+]i的变化是调节卵子活化的重要因素。成熟的海鞘卵在受精中期被捕获，受精后观察到两个系列的[Ca2+] I瞬变：受精时的Ca2+波（系列I）和第一极体和第二极体挤压之间的[Ca2+] I振荡（系列II）。我们研究了[Ca2+]i升高的机制，以及[Ca2+]i在琼脂树卵激活过程中的作用。抗IP3受体1型的单克隆抗体18A10能抑制IP3诱导的仓鼠和小鼠卵中Ca2+的释放，但对系列I或卵变形没有明显的抑制作用，而系列II和第一次细胞分裂则被该抗体抑制。钌红是一种ryanodine受体介导的Ca2+释放抑制剂，对[Ca2+]i瞬态和其他与卵子激活相关的事件没有明显的影响。

The inositol 1,4,5-triaphosphate (IP3) receptor (IP3R) acts as a Ca2+ release channel on internal Ca2+ stores. Type 1 IP3R(IP3R1) is enriched in growth cones of neurons in chick dorsal root ganglia. Depletion in internal Ca2+ stores and inhibition of IP3 signaling with drugs inhibited neurite extension. Microinjection of heparin, a competitive IP3R blocker, induced neurite retraction. Acute localized loss of function of IP3R1 in the growth cone induced by chromophore assisted laser inactivation resulted in growth cones arrest and neurite retraction. IP3-induced Ca2+ release in growth cones appears to have a crucial role in control of nerve growth.Changes in [Ca2+]i are an essential factor regulating egg activation. Matured ascidian eggs are arrested at metaphase I , and two series of [Ca2+]i transients have been observed after fertilization : Ca2+ waves just fertilization (Series I) and [Ca2+]i oscillation between the first and second polar body extrusion (Series II). We investigated mechanisms involved in the elevation of [Ca2+]i and the role of the [Ca2+]i transients during egg activation in Ciona savignyi. The monoclonal antibody 18A10 against IP3 receptor type 1, which inhibits IP3-induced Ca2+ release in hamster and mouse eggs, did not show substantial inhibitory effects on series I or egg deformation, whereas Series II and the first cell division were inhibited by the antibody. Ruthenium red, an inhibitor of ryanodine receptor-mediated Ca2+ release, had no apparent effect of [Ca2+]i transients and other events related to the egg activation.