Ko Juyeon, Kim Jinhyeong, Myeong Jongyun, Kwak Misun, So Insuk
Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.
Korean J Physiol Pharmacol. 2023 Mar 1;27(2):187-196. doi: 10.4196/kjpp.2023.27.2.187.
Transient receptor potential canonical (TRPC) channels are non-selective calcium-permeable cation channels. It is suggested that TRPC4β is regulated by phospholipase C (PLC) signaling and is especially maintained by phosphatidylinositol 4,5-bisphosphate (PIP). In this study, we present the regulation mechanism of the TRPC4 channel with PIP hydrolysis which is mediated by a channel-bound PLCδ1 but not by the GPCR signaling pathway. Our electrophysiological recordings demonstrate that the Ca via an open TRPC4 channel activates PLCδ1 in the physiological range, and it causes the decrease of current amplitude. The existence of PLCδ1 accelerated PIP depletion when the channel was activated by an agonist. Interestingly, PLCδ1 mutants which have lost the ability to regulate PIP level failed to reduce the TRPC4 current amplitude. Our results demonstrate that TRPC4 self-regulates its activity by allowing Ca ions into the cell and promoting the PIP hydrolyzing activity of PLCδ1.
瞬时受体电位香草酸亚型（TRPC）通道是一种非选择性的钙通透性阳离子通道。有研究表明，TRPC4β受磷脂酶C（PLC）信号通路调控，尤其受磷脂酰肌醇4,5-二磷酸（PIP）维持。在本研究中，我们展示了TRPC4通道通过PIP水解的调控机制，该水解由结合在通道上的PLCδ1介导，而非GPCR信号通路。我们的电生理记录表明，通过开放的TRPC4通道进入的钙离子在生理范围内激活PLCδ1，并导致电流幅度降低。当通道被激动剂激活时，PLCδ1的存在加速了PIP的消耗。有趣的是，丧失调节PIP水平能力的PLCδ1突变体无法降低TRPC4电流幅度。我们的结果表明，TRPC4通过允许钙离子进入细胞并促进PLCδ1的PIP水解活性来自我调节其活性。
