HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/2/R402    most recent 00488.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Herrera, G. M. Articles by Nelson, M. T. Search for Related Content PubMed PubMed Citation Articles by Herrera, G. M. Articles by Nelson, M. T.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Negative feedback regulation of nerve-mediated contractions by K_Ca channels in mouse urinary bladder smooth muscle

Department of Pharmacology, University of Vermont, Burlington, Vermont

Submitted 22 July 2004 ; accepted in final form 23 March 2005

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) Ca²⁺-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 Ca²⁺ 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.

potassium channel; incontinence; iberiotoxin; apamin; large- and small-conductance channels

This article has been cited by other articles:

				T. J. Heppner, M. E. Werner, B. Nausch, C. Vial, R. J. Evans, and M. T. Nelson Nerve-evoked purinergic signalling suppresses action potentials, Ca2+ flashes and contractility evoked by muscarinic receptor activation in mouse urinary bladder smooth muscle J. Physiol., November 1, 2009; 587(21): 5275 - 5288. [Abstract] [Full Text] [PDF]

				U. S. Lee and J. Cui {beta} subunit-specific modulations of BK channel function by a mutation associated with epilepsy and dyskinesia J. Physiol., April 1, 2009; 587(7): 1481 - 1498. [Abstract] [Full Text] [PDF]

				J. Layne, M. Werner, D. Hill-Eubanks, and M. Nelson NFATc3 regulates BK channel function in murine urinary bladder smooth muscle Am J Physiol Cell Physiol, September 1, 2008; 295(3): C611 - C623. [Abstract] [Full Text] [PDF]

				K. S. Thorneloe, A. M. Knorn, P. E. Doetsch, E. S. R. Lashinger, A. X. Liu, C. T. Bond, J. P. Adelman, and M. T. Nelson Small-conductance, Ca2+-activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1737 - R1743. [Abstract] [Full Text] [PDF]

				Y.-K. Ng, W. C. de Groat, and H.-Y. Wu Smooth muscle and neural mechanisms contributing to the downregulation of neonatal rat spontaneous bladder contractions during postnatal development Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R2100 - R2112. [Abstract] [Full Text] [PDF]

				M. E. Werner, A.-M. Knorn, A. L. Meredith, R. W. Aldrich, and M. T. Nelson Frequency encoding of cholinergic- and purinergic-mediated signaling to mouse urinary bladder smooth muscle: modulation by BK channels Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R616 - R624. [Abstract] [Full Text] [PDF]