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The regulation of transient receptor potential canonical 4 (TRPC4) channel by phosphodiesterase 5 inhibitor via the cyclic guanosine 3′5′-monophosphate

  • Ion channels, receptors and transporters
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Abstract

The transient receptor potential (TRP) protein superfamily consists of a diverse group of cation channels that bear structural similarities to the fruit fly Drosophila TRP. The TRP superfamily is distinct from other groups of ion channels in displaying a large diversity in ion selectivity, modes of activation, and physiological functions. Classical TRP (transient receptor potential canonical (TRPC)) channels are activated by stimulation of Gq-PLC-coupled receptors and modulated by phosphorylation. The cyclic guanosine monophosphate (cGMP)-PKG pathway is involved in the regulation of TRPC3 and TRPC6 channels. Phosphodiesterase (PDE) 5 inhibitor induced muscle relaxation in corporal smooth muscle cells and was used to treat erectile dysfunction by inhibiting cGMP degradation. Here, we report the functional relationship between TRPC4 and cGMP. In human embryonic kidney (HEK) 293 cells overexpressing TRPC4, cGMP selectively activated TRPC4 channels and increased cytosolic calcium level through TRPC4 channel. We investigated phosphorylation sites in TRPC4 channels and identified S688 as an important phosphorylation site for the cGMP-PKG pathway. Cyclic GMP also activated TRPC4-like current with doubly rectifying current-voltage relationship in prostate smooth muscle cell lines. Taken together, these results show that TRPC4 is phosphorylated by the cGMP-PKG pathway and might be an important target for modulating prostate function by PDE5 inhibitors.

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Acknowledgements

We thank Dr. M. Schaefer for providing the mouse TRPC4 cDNA, and Dr. Shuji Kaneko for providing the human TRPC5-GFP.

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Authors and Affiliations

  1. Department of Physiology, Seoul National University College of Medicine, 28 Yongon-dong Chongno-Gu, Seoul, 110-799, South Korea

    Jinhong Wie, SeungJoo Jeong, Misun Kwak, Jongyun Myeong & Insuk So

  2. Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea

    MeeRee Chae & Sung Won Lee

  3. Department of Urology, Chonbuk National University Medical School, Jeonju, South Korea

    Jong Kwan Park

  4. Institute for Medical Sciences, Chonbuk National University, Jeonju, South Korea

    Jong Kwan Park

  5. Institute and Clinical Trial Center of Medical Device, Chonbuk National University Hospital, Jeonju, South Korea

    Jong Kwan Park

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  1. Jinhong Wie
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Correspondence to Insuk So.

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Funding/support and role of the sponsor

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health &Welfare, Republic of Korea (HI13C0104).

Additional information

Jinhong Wie and SeungJoo Jeong contributed equally to this work

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Wie, J., Jeong, S., Kwak, M. et al. The regulation of transient receptor potential canonical 4 (TRPC4) channel by phosphodiesterase 5 inhibitor via the cyclic guanosine 3′5′-monophosphate. Pflugers Arch - Eur J Physiol 469, 693–702 (2017). https://doi.org/10.1007/s00424-017-1937-7

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  • DOI: https://doi.org/10.1007/s00424-017-1937-7

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