Liang Haoya, DeMaria Carla D, Erickson Michael G, Mori Masayuki X, Alseikhan Badr A, Yue David T
Ca2+ Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Neuron. 2003 Sep 11;39(6):951-60. doi: 10.1016/s0896-6273(03)00560-9.
L-type (CaV1.2) and P/Q-type (CaV2.1) calcium channels possess lobe-specific CaM regulation, where Ca2+ binding to one or the other lobe of CaM triggers regulation, even with inverted polarity of modulation between channels. Other major members of the CaV1-2 channel family, R-type (CaV2.3) and N-type (CaV2.2), have appeared to lack such CaM regulation. We report here that R- and N-type channels undergo Ca(2+)-dependent inactivation, which is mediated by the CaM N-terminal lobe and present only with mild Ca2+ buffering (0.5 mM EGTA) characteristic of many neurons. These features, together with the CaM regulatory profiles of L- and P/Q-type channels, are consistent with a simplifying principle for CaM signal detection in CaV1-2 channels-independent of channel context, the N- and C-terminal lobes of CaM appear invariably specialized for decoding local versus global Ca2+ activity, respectively.
L型（CaV1.2）和P/Q型（CaV2.1）钙通道具有叶特异性钙调蛋白（CaM）调节作用，即Ca2+与CaM的一个或另一个叶结合会触发调节，即使通道之间的调节极性相反。CaV1-2通道家族的其他主要成员，R型（CaV2.3）和N型（CaV2.2），似乎缺乏这种CaM调节。我们在此报告，R型和N型通道会经历Ca(2+)依赖性失活，这是由CaM的N端叶介导的，并且仅在许多神经元特有的轻度Ca2+缓冲（0.5 mM乙二醇双四乙酸）条件下出现。这些特征，连同L型和P/Q型通道的CaM调节概况，与CaV1-2通道中CaM信号检测的简化原则一致——与通道背景无关，CaM的N端和C端叶似乎分别始终专门用于解码局部与全局Ca2+活性。
