Gs cascade regulates canonical transient receptor potential 5 (TRPC5) through cAMP mediated intracellular Ca 2+ release and ion channel trafficking

Chansik Hong, Jinsung Kim, Jae Pyo Jeon, Jinhong Wie, Misun Kwak, Kotdaji Ha, Hana Kim, Jongyun Myeong, Sung Young Kim, Ju Hong Jeon, Insuk So

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Canonical transient receptor potential (TRPC) channels are Ca 2+-permeable, non-selective cation channels those are widely expressed in mammalian cells. Various molecules have been found to regulate TRPC both in vivo and in vitro, but it is unclear how heterotrimeric G proteins transmit external stimuli to regulate the activity of TRPC5. Here, we demonstrated that TRPC5 was potentiated by the Gα s regulatory pathway. Whole-cell TRPC5 current was significantly increased by β-adrenergic receptor agonist, isoproterenol (ISO, 246±36%, n=6), an activator of the adenylate cyclase, forskolin (FSK, 273±6%, n=5), or a membrane permeable cAMP analogue, 8-Br-cAMP (251±63%, n=7). In addition, robust Ca 2+ transient induced by isoproterenol was observed utilizing a Ca 2+ imaging technique. When intracellular [Ca 2+] i was buffered to 50nM, cAMP-induced potentiation was attenuated. We also found that the Ca 2+ release is mediated by IP 3 since intracellular IP 3 infusion attenuated the potentiation of TRPC5 by Gα s cascade. Finally, we identified that the membrane localization of TRPC5 was significantly increased by ISO (155±17%, n=3), FSK (172±39%, n=3) or 8-Br-cAMP (216±59%, n=3). In conclusion, these results suggest that the Gα s-cAMP pathway potentiates the activity of TRPC5 via facilitating intracellular Ca 2+ dynamics and increasing channel trafficking to the plasma membrane.

Original languageEnglish
Pages (from-to)105-111
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume421
Issue number1
DOIs
StatePublished - Apr 27 2012

Keywords

  • Beta-adrenergic receptor
  • Ca
  • CAMP
  • Gs
  • Isoproterenol
  • TRPC

Fingerprint

Dive into the research topics of 'Gs cascade regulates canonical transient receptor potential 5 (TRPC5) through cAMP mediated intracellular Ca 2+ release and ion channel trafficking'. Together they form a unique fingerprint.

Cite this