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: 286/6/C1246    most recent 00501.2003v1 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 (14) Citing Articles via Google Scholar Google Scholar Articles by Thorneloe, K. S. Articles by Nelson, M. T. Search for Related Content PubMed PubMed Citation Articles by Thorneloe, K. S. Articles by Nelson, M. T.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Properties of a tonically active, sodium-permeable current in mouse urinary bladder smooth muscle

Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vermont 05405

Submitted 14 November 2003 ; accepted in final form 14 January 2004

Urinary bladder smooth muscle (UBSM) elicits depolarizing action potentials, which underlie contractile events of the urinary bladder. The resting membrane potential of UBSM is approximately –40 mV and is critical for action potential generation, with hyperpolarization reducing action potential frequency. We hypothesized that a tonic, depolarizing conductance was present in UBSM, functioning to maintain the membrane potential significantly positive to the equilibrium potential for K⁺ (E_K; –85 mV) and thereby facilitate action potentials. Under conditions eliminating the contribution of K⁺ and voltage-dependent Ca²⁺ channels, and with a clear separation of cation- and Cl^–-selective conductances, we identified a novel background conductance (I_cat) in mouse UBSM cells. I_cat was mediated predominantly by the influx of Na⁺, although a small inward Ca²⁺ current was detectable with Ca²⁺ as the sole cation in the bathing solution. Extracellular Ca²⁺, Mg²⁺, and Gd³⁺ blocked I_cat in a voltage-dependent manner, with K_i values at –40 mV of 115, 133, and 1.3 µM, respectively. Although UBSM I_cat is extensively blocked by physiological extracellular Ca²⁺ and Mg²⁺, a tonic, depolarizing I_cat was detected at –40 mV. In addition, inhibition of I_cat demonstrated a hyperpolarization of the UBSM membrane potential and decreased the amplitude of phasic contractions of isolated UBSM strips. We suggest that I_cat contributes tonically to the depolarization of the UBSM resting membrane potential, facilitating action potential generation and thereby a maintenance of urinary bladder tone.

urinary bladder excitability; membrane potential; electrophysiology; cation channels; voltage-dependent ion channel block

This article has been cited by other articles:

				K. S. Thorneloe, A. C. Sulpizio, Z. Lin, D. J. Figueroa, A. K. Clouse, G. P. McCafferty, T. P. Chendrimada, E. S. R. Lashinger, E. Gordon, L. Evans, et al. N-((1S)-1-{[4-((2S)-2-{[(2,4-Dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a Novel and Potent Transient Receptor Potential Vanilloid 4 Channel Agonist Induces Urinary Bladder Contraction and Hyperactivity: Part I J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 432 - 442. [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]

				F.-W. Zhou, S. G. Matta, and F.-M. Zhou Constitutively Active TRPC3 Channels Regulate Basal Ganglia Output Neurons J. Neurosci., January 9, 2008; 28(2): 473 - 482. [Abstract] [Full Text] [PDF]

				V. P. Zagorodnyuk, P. Lynn, M. Costa, and S. J. H. Brookes Mechanisms of mechanotransduction by specialized low-threshold mechanoreceptors in the guinea pig rectum Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G397 - G406. [Abstract] [Full Text] [PDF]

				G. V. Petkov, O. B. Balemba, M. T. Nelson, and G. M. Mawe Identification of a spontaneously active, Na+-permeable channel in guinea pig gallbladder smooth muscle Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G501 - G507. [Abstract] [Full Text] [PDF]

				A. P Albert, A. S Piper, and W. A Large Role of phospholipase D and diacylglycerol in activating constitutive TRPC-like cation channels in rabbit ear artery myocytes J. Physiol., August 1, 2005; 566(3): 769 - 780. [Abstract] [Full Text] [PDF]

				D. J. Beech, K. Muraki, and R. Flemming Non-selective cationic channels of smooth muscle and the mammalian homologues of Drosophila TRP J. Physiol., September 15, 2004; 559(3): 685 - 706. [Abstract] [Full Text] [PDF]