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Gs cascade regulates canonical transient receptor potential 5 (TRPC5) through cAMP mediated intracellular Ca2+ release and ion channel trafficking

2012; Elsevier BV; Volume: 421; Issue: 1 Linguagem: Inglês

10.1016/j.bbrc.2012.03.123

1090-2104

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

Ion channel regulation and function

Canonical transient receptor potential (TRPC) channels are Ca2+-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 Gαs 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 Ca2+ transient induced by isoproterenol was observed utilizing a Ca2+ imaging technique. When intracellular [Ca2+]i was buffered to 50 nM, cAMP-induced potentiation was attenuated. We also found that the Ca2+ release is mediated by IP3 since intracellular IP3 infusion attenuated the potentiation of TRPC5 by Gαs 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 Gαs–cAMP pathway potentiates the activity of TRPC5 via facilitating intracellular Ca2+ dynamics and increasing channel trafficking to the plasma membrane.