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Updated: Jan 19, 2026
Purification of Endogenous Drosophila Transient Receptor Potential Channels
Published on: December 28, 2021
Identification of phospholipase C β downstream effect on transient receptor potential canonical 1/4, transient
Juyeon Ko1, Jongyun Myeong1,2, Misun Kwak1
1Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.
Abstract:
Gαq-coupled receptor stimulation was implied in the activation process of transient receptor potential canonical (TRPC)1/4 and TRPC1/5 heterotetrameric channels. The inactivation occurs due to phosphatidylinositol 4,5-biphosphate (PI(4,5)P2) depletion. When PI(4,5)P2 depletion was induced by muscarinic stimulation or inositol polyphosphate 5-phosphatase (Inp54p), however, the inactivation by muscarinic stimulation was greater compared to that by Inp54p. The aim of this study was to investigate the complete inactivation mechanism of the heteromeric channels upon Gαq-phospholipase C β (Gαq-PLCβ) activation. We evaluated the activity of heteromeric channels with electrophysiological recording in HEK293 cells expressing TRPC channels. TRPC1/4 and TRPC1/5 heteromers undergo further inhibition in PLCβ activation and calcium/protein kinase C (PKC) signaling. Nevertheless, the key factors differ. For TRPC1/4, the inactivation process was facilitated by Ca2+ release from the endoplasmic reticulum, and for TRPC1/5, activation of PKC was concerned mostly. We conclude that the subsequent increase in cytoplasmic Ca2+ due to Ca2+ release from the endoplasmic reticulum and activation of PKC resulted in a second phase of channel inhibition following PI(4,5)P2 depletion.
Insights
Gαq-coupled receptor activation of TRPC1/4 and TRPC1/5 channels involves phosphatidylinositol 4,5-biphosphate depletion. Further inhibition occurs via calcium release and protein kinase C activation, with distinct mechanisms for TRPC1/4 and TRPC1/5 heteromers.
Area of Science:
- Molecular biology
- Cell signaling
- Ion channel physiology
Background:
- Gαq-coupled receptor stimulation activates TRPC1/4 and TRPC1/5 channels.
- Channel inactivation is linked to phosphatidylinositol 4,5-biphosphate (PI(4,5)P2) depletion.
- Muscarinic stimulation causes greater inactivation than inositol polyphosphate 5-phosphatase (Inp54p).
Purpose of the Study:
- To elucidate the complete inactivation mechanism of TRPC1/4 and TRPC1/5 heteromeric channels upon Gαq-phospholipase C β (Gαq-PLCβ) activation.
- To differentiate the roles of calcium (Ca2+) release and protein kinase C (PKC) in channel inactivation.
Main Methods:
- Electrophysiological recordings in HEK293 cells expressing TRPC channels.
- Evaluation of heteromeric channel activity under various stimulation conditions.
Main Results:
- TRPC1/4 and TRPC1/5 heteromers show further inhibition upon Gαq-PLCβ activation.
- TRPC1/4 inactivation is facilitated by Ca2+ release from the endoplasmic reticulum.
- TRPC1/5 inactivation is primarily mediated by protein kinase C (PKC) activation.
- A second phase of channel inhibition occurs following PI(4,5)P2 depletion.
Conclusions:
- Distinct mechanisms involving Ca2+ release and PKC activation contribute to the second phase of TRPC1/4 and TRPC1/5 channel inhibition.
- Understanding these pathways is crucial for comprehending Gαq-coupled receptor signaling through TRPC channels.
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