Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder

Ayu Isogai, Ken Lee, Retsu Mitsui, Hikaru Hashitani

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We investigated the role of TRPV4 channels (TRPV4) in regulating the contractility of detrusor smooth muscle (DSM) and muscularis mucosae (MM) of the urinary bladder. Distribution of TRPV4 in DSM and MM of guinea-pig bladders was examined by fluorescence immunohistochemistry. Changes in the contractility of DSM and MM bundles were measured using isometric tension recording. Intracellular Ca2+ dynamics were visualized by Cal-520 fluorescent Ca2+ imaging, while membrane potential changes were recorded using intracellular microelectrode technique. DSM and MM expressed TRPV4 immunoreactivity. GSK1016790A (GSK, 1 nM), a TRPV4 agonist, evoked a sustained contraction in both DSM and MM associated with a cessation of spontaneous phasic contractions in a manner sensitive to HC-067047 (10 μM), a TRPV4 antagonist. Iberiotoxin (100 nM) and paxilline (1 μM), large conductance Ca2+-activated K+ (BK) channel blockers restored the spontaneous contractions in GSK. The sustained contractions in DSM and MM were reduced by nifedipine (10 μM), a blocker of L-type voltage-dependent Ca2+ channels (LVDCCs) by about 40 % and by nominally Ca2+-free solution by some 90 %. GSK (1 nM) abolished spontaneous Ca2+ transients, increased basal Ca2+ levels and also prevented spontaneous action potential discharge associated with DSM membrane hyperpolarization. In conclusion, Ca2+ influx through TRPV4 appears to activate BK channels to suppress spontaneous contractions and thus a functional coupling of TRPV4 with BK channels may act as a self-limiting mechanism for bladder contractility during its storage phase. Despite the membrane hyperpolarization in GSK, Ca2+ entry mainly through TRPV4 develops the tonic contraction.

Original languageEnglish
Pages (from-to)1573-1585
Number of pages13
JournalPflugers Archiv European Journal of Physiology
Volume468
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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