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(+) (E(K); -85 mV) and thereby facilitate action potentials. Under conditions eliminating the contribution of K(+) and voltage-dependent Ca(2+) 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 Ca(2+) current was detectable with Ca(2+) as the sole cation in the bathing solution. Extracellular Ca(2+), Mg(2+), and Gd(3+) blocked I(cat) in a voltage-dependent manner, with K(i) values at -40 mV of 115, 133, and 1.3 microM, respectively. Although UBSM I(cat) is extensively blocked by physiological extracellular Ca(2+) and Mg(2+), 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.

Constitutively Active TRPC3 Channels Regulate Basal Ganglia Output Neurons

“…These results indicate that extracellular Gd 3ϩ can inhibit the tonically active, voltage-independent inward current in SNr GABA neurons, consistent with our idea that TRPC3 channels may be mediating the tonic inward current and with published reports that native TRPC3 channels are inhibited by extracellular gadolinium (Thorneloe and Nelson, 2004;Albert et al, 2006).…”

“…The effects of 100 M Gd 3ϩ on membrane potential and the tonic inward current were also reduced by ϳ80% when extracellular Na ϩ was reduced by 125 mM (n ϭ 3), indicating the Gd 3ϩ -sensitive tonic inward current was also dependent on Na ϩ . These data further support our hypothesis that the tonic inward current was probably mediated by TRPC3 channels because Na ϩ is known to carry the majority of the FFA-and Gd 3ϩ -sensitive, native TRPC3 channel-mediated current (Thorneloe and Nelson, 2004;Albert et al, 2006).…”

“…It was also inhibited by extracellular Ca 2ϩ and Gd 3ϩ , also causing hyperpolarization. These biophysical and pharmacological characteristics are similar or identical to those of native TRPC3 channels in other cell systems (Clapham, 2003;Thorneloe and Nelson, 2004;Petkov et al, 2005;Albert et al, 2006;Ramsey et al, 2006;Hardie, 2007;Venkatachalam and Montell, 2007).…”

“…2؉ inhibits the tonic depolarization and inward current in SNr GABA neurons Extracellular Ca 2ϩ is known to inhibit TRPC3 channel while enhancing the activity of other types of TRP channels (Thorneloe and Nelson, 2004;Albert et al, 2006). Our data presented above indicate that TRPC3 channels may mediate the tonic inward current in SNr GABA neurons.…”

“…Because Na ϩ is a main extracellular cation that is permeable to native TRP channels (Thorneloe and Nelson, 2004;Albert et al, 2006), we hypothesized that Na ϩ is the main cation carrying the tonic inward current in SNr GABA neurons.…”