Negative feedback regulation of nerve-mediated contractions by KCa channels in mouse urinary bladder smooth muscle.
When the urinary bladder is full, activation of parasympathetic nerves causes release of neurotransmitters that induce forceful contraction of the detrusor muscle, leading to urine voiding. The roles of ion channels that regulate contractility of urinary bladder smooth muscle (UBSM) in response to activation of parasympathetic nerves are not well known. The present study was designed to characterize the role of large (BK)- and small-conductance (SK) Ca(2+)-activated K(+) (K(Ca)) channels in regulating UBSM contractility in response to physiological levels of nerve stimulation in UBSM strips from mice. Nerve-evoked contractions were induced by electric field stimulation (0.5-50 Hz) in isolated strips of UBSM. BK and SK channel inhibition substantially increased the amplitude of nerve-evoked contractions up to 2.45 +/- 0.12- and 2.99 +/- 0.25-fold, respectively. When both SK and BK channels were inhibited, the combined response was additive. Inhibition of L-type voltage-dependent Ca(2+) channels (VDCCs) in UBSM inhibited nerve-evoked contractions by 92.3 +/- 2.0%. These results suggest that SK and BK channels are part of two distinct negative feedback pathways that limit UBSM contractility in response to nerve stimulation by modulating the activity of VDCCs. Dysfunctional regulation of UBSM contractility by alterations in BK/SK channel expression or function may underlie pathologies such as overactive bladder.
Herrera
Gerald M
GM
Dept. of Pharmacology, University of Vermont, Burlington, VT 05405, USA.
Etherton
Bud
B
Nausch
Bernhard
B
Nelson
Mark T
MT
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004357:Drug Synergism; D004558:Electric Stimulation; D025461:Feedback, Physiological; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000502:physiology*; D001743:Urinary Bladder / Q000502:physiology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D001030:Apamin; C064719:iberiotoxin; D002217:Carbachol; D004110:Diltiazem