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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

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