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Identification of phospholipase Cβ downstream effect on transient receptor potential canonical 1/4, transient receptor potential canonical 1/5 channels

  • Ko, Juyeon (Department of Physiology, Seoul National University College of Medicine) ;
  • Myeong, Jongyun (Department of Physiology, Seoul National University College of Medicine) ;
  • Kwak, Misun (Department of Physiology, Seoul National University College of Medicine) ;
  • Jeon, Ju-Hong (Department of Physiology, Seoul National University College of Medicine) ;
  • So, Insuk (Department of Physiology, Seoul National University College of Medicine)
  • Received : 2019.06.17
  • Accepted : 2019.07.26
  • Published : 2019.09.01

Abstract

$G{\alpha}_q$-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 ($PI(4,5)P_2$) depletion. When $PI(4,5)P_2$ 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 $G{\alpha}_q$-phospholipase $C{\beta}$ ($G{\alpha}_q-PLC{\beta}$) 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 $PLC{\beta}$ activation and calcium/protein kinase C (PKC) signaling. Nevertheless, the key factors differ. For TRPC1/4, the inactivation process was facilitated by $Ca^{2+}$ release from the endoplasmic reticulum, and for TRPC1/5, activation of PKC was concerned mostly. We conclude that the subsequent increase in cytoplasmic $Ca^{2+}$ due to $Ca^{2+}$ release from the endoplasmic reticulum and activation of PKC resulted in a second phase of channel inhibition following $PI(4,5)P_2$ depletion.

Keywords

References

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