Zamponi Gerald W, Snutch Terrance P
Department of Physiology and Biophysics, University of Calgary, Canada.
Mol Interv. 2002 Dec;2(8):476-8. doi: 10.1124/mi.2.8.476.
The activity of some voltage-gated calcium channels (VGCCs) can be inhibited by specific G protein beta subunits. Conversely, in the case of N-type VGCCs, protein kinase C can relieve Gbeta-dependent inhibition by phosphorylating at least one specific site on the calcium channel. A recent publication describes a newly identified method of intracellular regulation of specific VGCCs. Wu et al. have uncovered that VGCC activity can be regulated by phosphatidylinositol-4',5'-bisphosphate (PIP2). Whereas PIP2 is important for maintaining the activity (open state) of Cav2.1 (N-type) and Cav2.2 (P/Q-type) channels, the enzymatic breakdown of PIP2 leads to the inactivation of these channels. Additionally, PIP2 can cause changes in voltage-dependent activation of Cav2.2 (P/Q-type) channels that make it more difficult for these channels to open (from the closed state). Furthermore, protein kinase A activity can circumvent PIP2-mediated inhibition. Thus, the PIP2-mediated regulation of VGCCs is tightly controlled by the functions of kinases (and phosphatases), as well as phospholipases. Wu et al. stress that because PIP2 can be found at synapses, PIP2-dependent control of VGCCs "could have profound consequences on synaptic transmission and plasticity."
某些电压门控性钙通道（VGCCs）的活性可被特定的G蛋白β亚基抑制。相反，就N型VGCCs而言，蛋白激酶C可通过磷酸化钙通道上的至少一个特定位点来解除Gβ依赖性抑制。最近的一篇出版物描述了一种新发现的特定VGCCs细胞内调节方法。吴等人发现VGCC活性可受磷脂酰肌醇-4',5'-二磷酸（PIP2）调节。虽然PIP2对于维持Cav2.1（N型）和Cav2.2（P/Q型）通道的活性（开放状态）很重要，但PIP2的酶促分解会导致这些通道失活。此外，PIP2可引起Cav2.2（P/Q型）通道电压依赖性激活的变化，使这些通道更难打开（从关闭状态）。此外，蛋白激酶A的活性可规避PIP2介导的抑制。因此，激酶（和磷酸酶）以及磷脂酶的功能对PIP2介导的VGCCs调节进行了严格控制。吴等人强调，由于在突触中可发现PIP2，PIP2依赖性的VGCCs控制“可能对突触传递和可塑性产生深远影响”。
