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Characterization and functional roles of KCNQ-encoded voltage-gated potassium (Kv7) channels in human corpus cavernosum smooth muscle

Pflügers Archiv - European Journal of Physiology volume 472, pages 89–102 (2020)Cite this article

Abstract

The group of KCNQ-encoded voltage-gated potassium (Kv7) channels includes five family members (Kv7.1–7.5). We examined the molecular expression and functional roles of Kv7 channels in corporal smooth muscle (CSM). Isolated rabbit CSM strips were mounted in an organ bath system to characterize Kv7 channels during CSM relaxation. Intracellular Ca2+ levels were measured in the CSM using the Ca2+ dye Fluo-4 AM. The expression of the KCNQ1–5 (the encoding genes for Kv7.1–7.5) and KCNE1–5 subtypes was determined by quantitative real-time PCR. Electrophysiological recordings and an in situ proximity ligation assay (PLA) were also performed. ML213 (a Kv7.2/7.4/7.5 activator) exhibited the most potent relaxation effect. XE911 (a Kv7.1–7.5 blocker) significantly inhibited the relaxation caused by ML213. Removal of the endothelium from the CSM did not affect the relaxation effect of ML213. H-89 (a protein kinase A inhibitor) and ESI-09 (an exchange protein directly activated by cAMP inhibitor) significantly inhibited ML213-induced relaxation (H-89: 31.3%; ESI-09: 52.7%). XE991 significantly increased basal [Ca2+]i in hCSM cells. KCNQ4 (the Kv7.4-encoding gene) and KCNE4 in CSM were the most abundantly expressed subtypes in humans and rats, respectively. KCNQ4 and KCNE4 expression was significantly decreased in diabetes mellitus rats. ML213 significantly increased the outward current amplitude. XE991 inhibited the ML213-induced outward currents. ML213 hyperpolarized the hCSM cell membrane potential. Subsequent addition of XE991 completely reversed the ML213-induced hyperpolarizing effects. A combination of Kv7.4 and Kv7.5 antibodies generated a strong PLA signal. We found that the Kv7.4 channel is a potential target for ED treatment.

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Funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C0982).

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Authors and Affiliations

  1. Department of Urology, National Police Hospital, Seoul, South Korea

    Jun Ho Lee

  2. Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea

    Mee Ree Chae, Su Jeong Kang, Hyun Hwan Sung, Deok Hyun Han & Sung Won Lee

  3. Department of Physiology and Biophysics, Seoul National University College of Medicine, Seoul, South Korea

    Insuk So

  4. Department of Urology, Medical School, and Institute for Medical Sciences, Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Chonbuk National University, Jeonju, South Korea

    Jong Kwan Park

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  1. Jun Ho Lee
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Lee, J.H., Chae, M.R., Kang, S.J. et al. Characterization and functional roles of KCNQ-encoded voltage-gated potassium (Kv7) channels in human corpus cavernosum smooth muscle. Pflugers Arch - Eur J Physiol 472, 89–102 (2020). https://doi.org/10.1007/s00424-019-02343-7

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  • DOI: https://doi.org/10.1007/s00424-019-02343-7

Keywords

  • Corpus cavernosum
  • Erectile dysfunction
  • KCNQ
  • KCNE
  • Kv7.4 channel