[BK channels play an important role as a negative feedback mechanism in the regulation of spontaneous rhythmic contraction of urinary bladder smooth muscles].
Smooth muscles of urinary bladder wall exhibit spontaneous rhythmic contraction which is myogenic in origin. Although the precise mechanism responsible for the generation of this mechanical activity remains to be established, it can be related closely to the action potential (AP) in urinary bladder smooth muscle (UBSM) cell, and may be the fundamental constituent to determine urinary bladder physiological functions to store and micturate urine. In the present study, possible roles of voltage-dependent and Ca(2+)-sensitive K+ (BK) channels, highly expressed in UBSM cells, were examined in the regulation of spontaneous UBSM contraction with reference to the generation of AP. Iberiotoxin (IbTx), a selective BK channel blocker, strongly increased mechanical activity and AP generation in guinea-pig UBSM. In contrast, BK channel openers (NS-1619, niflumic acid; estradiol, tamoxifen: BK channel alpha- and beta-subunit activators, respectively) significantly diminished AP generation and spontaneous mechanical activity. The present study indicates that BK channels play the primary role as a negative feedback element to limit extracellular Ca2+ influx through affecting AP configurations in the generation of UBSM contraction. BK channel openers including beta-subunit activators may be a potentially useful therapeutic remedy for the treatment of urinary bladder dysfunctions such as frequent urination.
Tanaka
Yoshio
Y
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Miyama 2-2-1, Funabashi-City, Chiba 274-8510, Japan.
Horinouchi
Takahiro
T
Tanaka
Hikaru
H
Shigenobu
Koki
K
Koike
Katsuo
K
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D025461:Feedback, Physiological / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009544:Niflumic Acid / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D001562:Benzimidazoles; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; C086491:NS 1619; D009544:Niflumic Acid; C064719:iberiotoxin