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

  • Jun Ho Lee
  • Mee Ree Chae
  • Su Jeong Kang
  • Hyun Hwan Sung
  • Deok Hyun Han
  • Insuk So
  • Jong Kwan Park
  • Sung Won LeeEmail author
Ion channels, receptors and transporters
  • 61 Downloads
Part of the following topical collections:
  1. Ion channels, receptors and transporters
  2. Ion channels, receptors and transporters

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.

Keywords

Corpus cavernosum Erectile dysfunction KCNQ KCNE Kv7.4 channel 

Notes

Funding information

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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • Jun Ho Lee
    • 1
  • Mee Ree Chae
    • 2
  • Su Jeong Kang
    • 2
  • Hyun Hwan Sung
    • 2
  • Deok Hyun Han
    • 2
  • Insuk So
    • 3
  • Jong Kwan Park
    • 4
  • Sung Won Lee
    • 2
    Email author
  1. 1.Department of UrologyNational Police HospitalSeoulSouth Korea
  2. 2.Department of Urology, Samsung Medical Center, Samsung Biomedical Research InstituteSungkyunkwan University School of MedicineSeoulSouth Korea
  3. 3.Department of Physiology and BiophysicsSeoul National University College of MedicineSeoulSouth Korea
  4. 4.Department of Urology, Medical School, and Institute for Medical Sciences, Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University HospitalChonbuk National UniversityJeonjuSouth Korea

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