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

Abstract

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+ ( EK; −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 ( Icat) in mouse UBSM cells. Icat 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 Icat in a voltage-dependent manner, with Ki values at −40 mV of 115, 133, and 1.3 μM, respectively. Although UBSM Icat is extensively blocked by physiological extracellular Ca2+ and Mg2+, a tonic, depolarizing Icat was detected at −40 mV. In addition, inhibition of Icat demonstrated a hyperpolarization of the UBSM membrane potential and decreased the amplitude of phasic contractions of isolated UBSM strips. We suggest that Icat contributes tonically to the depolarization of the UBSM resting membrane potential, facilitating action potential generation and thereby a maintenance of urinary bladder tone.