title: Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder.
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 Ca(2+) dynamics were visualized by Cal-520 fluorescent Ca(2+) 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 Ca(2+)-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 Ca(2+) channels (LVDCCs) by about 40 % and by nominally Ca(2+)-free solution by some 90 %. GSK (1 nM) abolished spontaneous Ca(2+) transients, increased basal Ca(2+) levels and also prevented spontaneous action potential discharge associated with DSM membrane hyperpolarization. In conclusion, Ca(2+) 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, Ca(2+) entry mainly through TRPV4 develops the tonic contraction.
authors: Department of Cell Physiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, 467-8601, Japan.
authors: Ayu
authors: A
authors: Isogai
authors: Department of Cell Physiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, 467-8601, Japan.|Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Ken
authors: K
authors: Lee
authors: Department of Cell Physiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, 467-8601, Japan.
authors: Retsu
authors: R
authors: Mitsui
authors: Department of Cell Physiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, 467-8601, Japan. hasitani@med.nagoya-cu.ac.jp.
authors: Hikaru
authors: H
authors: Hashitani
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009119:Muscle Contraction; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011758:Pyrroles / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000819:agonists / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism* / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; C573308:HC-067047; D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009025:Morpholines; D010455:Peptides; D026902:Potassium Channel Blockers; D011758:Pyrroles; D050916:TRPV Cation Channels; C048220:paxilline; C064719:iberiotoxin; D009543:Nifedipine
keywords: BK channels; Detrusor smooth muscle; Muscularis mucosae; Spontaneous contractions; TRPV4 channels