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Original Article

Korean J Physiol Pharmacol 2023; 27(2): 187-196

Published online March 1, 2023

Copyright © Korean J Physiol Pharmacol.

Negative self-regulation of transient receptor potential canonical 4 by the specific interaction with phospholipase C-δ1

Juyeon Ko#, Jinhyeong Kim#, Jongyun Myeong, Misun Kwak, and Insuk So*

Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea

Correspondence to:Insuk So

#These authors contributed equally to this work.

Author contributions: J. Ko designed the study, performed experiments, generated figures, analyzed data, and wrote the manuscript. J. Kim. generated figures and wrote the manuscript. J.M. performed confocal imaging, and M.K. performed Co-IP experiment. I.S. provided the overall experimental advice and coordinated the study. All authors reviewed the manuscript.

Received: November 26, 2022; Revised: December 27, 2022; Accepted: December 29, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 (PIP2). In this study, we present the regulation mechanism of the TRPC4 channel with PIP2 hydrolysis which is mediated by a channel-bound PLCδ1 but not by the GqPCR signaling pathway. Our electrophysiological recordings demonstrate that the Ca2+ via an open TRPC4 channel activates PLCδ1 in the physiological range, and it causes the decrease of current amplitude. The existence of PLCδ1 accelerated PIP2 depletion when the channel was activated by an agonist. Interestingly, PLCδ1 mutants which have lost the ability to regulate PIP2 level failed to reduce the TRPC4 current amplitude. Our results demonstrate that TRPC4 self-regulates its activity by allowing Ca2+ ions into the cell and promoting the PIP2 hydrolyzing activity of PLCδ1.

Keywords: Calcium, Fluorescence resonance energy transfer, Phosphatidylinositols, Phospholipase C delta, Transient receptor potential channels