title: Dynamics of receptor-operated Ca(2+) currents through TRPC channels controlled via the PI(4,5)P2-PLC signaling pathway.
abstract: Transient receptor potential canonical (TRPC) channels are Ca(2+)-permeable, nonselective cation channels that carry receptor-operated Ca(2+) currents (ROCs) triggered by receptor-induced, phospholipase C (PLC)-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Within the vasculature, TRPC channel ROCs contribute to smooth muscle cell depolarization, vasoconstriction, and vascular remodeling. However, TRPC channel ROCs exhibit a variable response to receptor-stimulation, and the regulatory mechanisms governing TRPC channel activity remain obscure. The variability of ROCs may be explained by their complex regulation by PI(4,5)P2 and its metabolites, which differentially affect TRPC channel activity. To resolve the complex regulation of ROCs, the use of voltage-sensing phosphoinositide phosphatases and model simulation have helped to reveal the time-dependent contribution of PI(4,5)P2 and the possible role of PI(4,5)P2 in the regulation of ROCs. These approaches may provide unprecedented insight into the dynamics of PI(4,5)P2 regulation of TRPC channels and the fundamental mechanisms underlying transmembrane ion flow. Within that context, we summarize the regulation of TRPC channels and their coupling to receptor-mediated signaling, as well as the application of voltage-sensing phosphoinositide phosphatases to this research. We also discuss the controversial bidirectional effects of PI(4,5)P2 using a model simulation that could explain the complicated effects of PI(4,5)P2 on different ROCs.
authors.affiliation: Department of Synthetic and Biological Chemistry, School of Engineering, Kyoto University Kyoto, Japan.
authors.forename: Masayuki X
authors.initials: MX
authors.lastname: Mori
authors.affiliation: Faculty of Dental Science, Kyushu University Fukuoka, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Itsuki
authors.affiliation: Department of Synthetic and Biological Chemistry, School of Engineering, Kyoto University Kyoto, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Hase
authors.affiliation: Department of Synthetic and Biological Chemistry, School of Engineering, Kyoto University Kyoto, Japan.
authors.forename: Seishiro
authors.initials: S
authors.lastname: Sawamura
authors.affiliation: Department of Synthetic and Biological Chemistry, School of Engineering, Kyoto University Kyoto, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Kurokawa
authors.affiliation: Department of Synthetic and Biological Chemistry, School of Engineering, Kyoto University Kyoto, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Department of Physiology, School of Medicine, Fukuoka University Fukuoka, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Inoue
keywords: Ca2+ signaling; PIP2; TRPC channels; receptor-operated calcium current; smooth muscle; voltage-sensing phosphatase