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

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• 作者：Chansik Hong^a ; ¹ ; Jinsung Kim^a ; ^b ; ¹ ; Jae-Pyo Jeon^a ; Jinhong Wie^a ; Misun Kwak^a ; Kotdaji Ha^a ; Hana Kim^a ; Jongyun Myeong^a ; Sung Young Kim^a ; Ju-Hong Jeon^a ; Insuk So^a ; ^{insuk@snu.ac.kr}
• 关键词：TRPC ; Gs ; Beta-adrenergic receptor ; Isoproterenol ; cAMP ; Ca2+
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：27 April, 2012
• 卷：421
• 期：1
• 页码：105-111
• 文件大小：1132 K

摘要

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 G伪_s regulatory pathway. Whole-cell TRPC5 current was significantly increased by 尾-adrenergic receptor agonist, isoproterenol (ISO, 246 卤 36%, n = 6), an activator of the adenylate cyclase, forskolin (FSK, 273 卤 6%, n = 5), or a membrane permeable cAMP analogue, 8-Br-cAMP (251 卤 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 G伪_s cascade. Finally, we identified that the membrane localization of TRPC5 was significantly increased by ISO (155 卤 17%, n = 3), FSK (172 卤 39%, n = 3) or 8-Br-cAMP (216 卤 59%, n = 3). In conclusion, these results suggest that the G伪_s-cAMP pathway potentiates the activity of TRPC5 via facilitating intracellular Ca²⁺ dynamics and increasing channel trafficking to the plasma membrane.