Identification of phospholipase C β downstream effect on transient receptor potential canonical 1/4, transient receptor potential canonical 1/5 channels
10.4196/kjpp.2019.23.5.357
- Author:
Juyeon KO
1
;
Jongyun MYEONG
;
Misun KWAK
;
Ju Hong JEON
;
Insuk SO
Author Information
1. Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea. insuk@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Calcium;
GTP-binding proteins;
Protein kinase C;
Transient receptor potential channels;
Type C phospholipases
- MeSH:
Calcium;
Cytoplasm;
Endoplasmic Reticulum;
GTP-Binding Proteins;
HEK293 Cells;
Inositol;
Phosphatidylinositol 4,5-Diphosphate;
Phospholipases;
Phosphotransferases;
Protein Kinase C;
Transient Receptor Potential Channels;
Type C Phospholipases
- From:The Korean Journal of Physiology and Pharmacology
2019;23(5):357-366
- CountryRepublic of Korea
- Language:English
-
Abstract:
Gα(q)-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 Gα(q)-phospholipase C β (Gα(q)-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.
