Key role for Kv11.1 (ether-a-go-go related gene) channels in rat bladder contractility

Vincenzo Barrese, Zena Wehbe, Alice Linden, Sarah McDowell, Elizabeth Forrester, Oleksander Povstyan, Karen D. McCloskey, Iain A. Greenwood*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
240 Downloads (Pure)

Abstract

In addition, to their established role in cardiac myocytes and neurons, ion channels encoded by ether-a-go-go-related genes (ERG1-3 or kcnh2,3 and 6) (kcnh2) are functionally relevant in phasic smooth muscle. The aim of the study was to determine the expression and functional impact of ERG expression products in rat urinary bladder smooth muscle using quantitative polymerase chain reaction, immunocytochemistry, whole-cell patch-clamp and isometric tension recording. kcnh2 was expressed in rat bladder, whereas kcnh6 and kcnh3 expression were negligible. Immunofluorescence for the kcnh2 expression product Kv11.1 was detected in the membrane of isolated smooth muscle cells. Potassium currents with voltage-dependent characteristics consistent with Kv11.1 channels and sensitive to the specific blocker E4031 (1 μM) were recorded from isolated detrusor smooth muscles. Disabling Kv11.1 activity with specific blockers (E4031 and dofetilide, 0.2–20 μM) augmented spontaneous contractions to a greater extent than BKCa channel blockers, enhanced carbachol-driven activity, increased nerve stimulation-mediated contractions, and impaired β-adrenoceptor-mediated inhibitory responses. These data establish for the first time that Kv11.1 channels are key determinants of contractility in rat detrusor smooth muscle.

Original languageEnglish
Article numbere15583
JournalPhysiological reports
Volume11
Issue number3
DOIs
Publication statusPublished - 07 Feb 2023

Bibliographical note

Funding Information:
We would like to acknowledge the help with immunocytochemistry from Dr. Alice Esseola and Sandra Ashton.

Publisher Copyright:
© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Keywords

  • BK channels
  • detrusor smooth muscle
  • ether-a-go-go-related genes
  • kcnh2 gene
  • Kv11.1

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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