Schneggenburger Ralf, Neher Erwin
AG Synaptische Dynamik & Modulation and Abt. Membranbiophysik, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg 11, D-37077 Göttingen, Germany.
Curr Opin Neurobiol. 2005 Jun;15(3):266-74. doi: 10.1016/j.conb.2005.05.006.
Vesicle fusion and transmitter release at synapses is driven by a highly localized Ca2+ signal that rapidly builds up around open Ca2+-channels at and near presynaptic active zones. It has been difficult to estimate the amplitude and the kinetics of this 'microdomain' signal by direct Ca2+-imaging approaches. Recently, Ca2+ uncaging at large CNS synapses, among them the calyx of Held, has shown that the intrinsic cooperativity of Ca2+ in inducing vesicle fusion is high, with 4-5 Ca2+ ions needed to trigger vesicle fusion. Given the Ca2+-sensitivity of vesicle fusion as determined by Ca2+-uncaging, it was found that a surprisingly small (10-25 microM) and brief (<1 ms) local Ca2+ signal is sufficient to achieve the amount, and the kinetics of the physiological transmitter release. The high cooperativity of Ca2+ in inducing vesicle fusion and the non-saturation of the Ca2+-sensor for vesicle fusion renders small changes of the local Ca2+-signal highly effective in changing the release probability; an insight that is important for our understanding of short-term modulation of synaptic strength.
突触处的囊泡融合和神经递质释放是由高度局部化的Ca2+信号驱动的，该信号在突触前活动区及其附近的开放Ca2+通道周围迅速形成。通过直接Ca2+成像方法来估计这种“微区”信号的幅度和动力学一直很困难。最近，在包括Held壶腹在内的大型中枢神经系统突触处进行的Ca2+光解笼实验表明，Ca2+诱导囊泡融合的内在协同性很高，触发囊泡融合需要4 - 5个Ca2+离子。根据Ca2+光解笼实验确定的囊泡融合对Ca2+的敏感性，发现一个小得出奇（10 - 25微摩尔）且短暂（<1毫秒）的局部Ca2+信号就足以实现生理递质释放的量和动力学。Ca2+诱导囊泡融合的高协同性以及囊泡融合的Ca2+传感器的不饱和性使得局部Ca2+信号的微小变化在改变释放概率方面非常有效；这一见解对于我们理解突触强度的短期调节很重要。
