Voltage-sensing phosphatase reveals temporal regulation of TRPC3/C6/C7 channels by membrane phosphoinositides

Kyohei Itsuki, Yuko Imai, Yasushi Okamura, Kihachiro Abe, Ryuji Inoue, Masayuki X. Mori

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

TRPC3/C6/C7 channels, a subgroup of classical/canonical TRP channels, are activated by diacylglycerol produced via activation of phospholipase C (PLC)-coupled receptors. Recognition of the physiological importance of these channels has been steadily growing, but the mechanism by which they are regulated remains largely unknown. We recently used a membrane-resident Danio rerio voltage-sensing phosphatase (DrVSP) to study TRPC3/C6/C7 regulation and found that the channel activity was controlled by PtdIns(4,5) P2-DAG signaling in a self-limiting manner (Imai Y et al. The Journal of Physiology 2012). In this addendum, we present the advantages of using DrVSP as a molecular tool to study PtdIns(4,5)P2 regulation. DrVSP should be readily applicable for studying phosphoinositide metabolism-linked channel regulation as well as lipid dynamics. Furthermore, in comparison to other modes of self-limiting ion channel regulation, the regulation of TRPC3/C6/C7 channels seems highly susceptible to activation signal strength, which could potentially affect both open duration and the time to peak activation and inactivation. Dysfunction of such self-limiting regulation may contribute to the pathology of the cardiovascular system, gastrointestinal tract and brain, as these channels are broadly distributed and affected by numerous neurohormonal agonists.

Original languageEnglish
Pages (from-to)206-209
Number of pages4
JournalChannels
Volume6
Issue number3
DOIs
Publication statusPublished - 2012

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry

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