Investigations into the spontaneous activity in smooth muscles of the lower urinary tract

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Spontaneous increases in [Ca^<2+>]_i (Ca^<2+> transients) preferentially originated along the boundary of muscle bundles and then spread to the other boundary (Ca^<2+> waves). The synchronicity of Ca^<2+> waves across the detrusor smooth muscle bundles was disrupted by 18β-glycyrrhetinic acid or carbenoxolone, while CPA, ryanodine, xestospongin C and U-73122 had no effect. Nifedipine but not nominal Ca^<2+> free solution diminished the synchronicity of Ca^<2+> waves before preventing their generation. Staining for c-kit identified interstitial cells (IC) located along both boundaries of muscle bundles. IC were more dominantly distributed in connective tissue between muscle bundles. IC generated nifedipine-resistant spontaneous Ca^<2+> transients, which occurred independently of those of smooth muscles. In conclusion, the propagation of Ca^<2+> transients in the bladder appears to be exclusively mediated by the spread of action potentials through gap junctions being facilitated by the r … More egenerative nature of L-type Ca^<2+> channels, without significant contribution of intracellular Ca^<2+> stores. IC in the bladder may modulate the transmission of Ca^<2+> transients originating from smooth muscle cells rather than being the pacemaker of spontaneous activity.To investigate the cellular mechanisms underlying spontaneous excitation of smooth muscle of the guinea-pig urinary bladder, isometric tension was measured in muscle bundles while recording the membrane potential from a cell in the bundle with a microelectrode. Changes in the intracellular calcium concentration [Ca^<2+>]_i (Ca^<2+> transients) were recorded in strips loaded with the fluorescent dye. Carbachol increased the frequency of action potentials and corresponding contractions. Apamin potentiated bursting activity and enhanced phasic contraction. Charybdotoxin induced prolonged action potentials that generated enlarged contractions. In contrast, levcromakalim reduced the frequency of action potentials, action potential bursts and the size of the contractions. Forskolin, 8-bromoguanosin 3', 5' cyclic monophosphate and Y-26763 suppressed contractions without reducing the amplitude of either action potentials or Ca^<2+> transients. These results confirm that action potentials and associated calcium transients are fundamental mechanisms in generating spontaneous contractions in smooth muscles of the guinea-pig bladder. However, in parallel with the excitation-contraction coupling, the sensitivity of the contractile proteins for Ca^<2+> may play an important role in regulating spontaneous excitation and can be modulated by cyclic nucleotides and Rho kinase. Less