Role of K+ Channels in Regulating Spontaneous Activity in Detrusor Smooth Muscle In Situ in the Mouse Bladder

Purpose: We investigated the functional role of K+ channels for regulating spontaneous activity in mouse bladder detrusor smooth muscle. Materials and Methods: The effects of different K+ channels blockers on spontaneous changes in membrane potential and intracellular Ca2+ dynamics were examined using intracellular recording techniques and Ca2+ imaging with fluo-4 fluorescence, respectively. Results: Detrusor smooth muscle generated spontaneous action potentials and Ca2+ transients. Iberiotoxin (0.1 mu M), charybdotoxin (0.1 mu M) or tetraethylammonium (I mM) increased the amplitude of action potentials and prolonged their repolarizing phase without inhibiting their after-hyperpolarization. Tetraethylammonium (10 mM) but not stromatoxin (0.1 mu M) suppressed after-hyperpolarization and further increased the amplitude and half duration of action potentials. Apamin (0.1 mu M) increased the frequency of action potentials but had no effect on their configuration. Spontaneous Ca2+ transients were generated in individual detrusor smooth muscle cells and occasionally propagated to neighboring cells to form intercellular Ca2+ waves. Transmural nerve stimulations invariably initiated synchronous Ca2+ transients within and across muscle bundles. Charybdotoxin (0.1 mu M) increased the amplitude of spontaneous Ca2+ transients, while the subsequent application of tetraethylammonium (10 mM) increased their half duration. In addition, tetraethylammonium increased the synchronicity of Ca2+ transients in muscle bundles. Conclusions: These results suggest that large and intermediate conductance Ca2+ activated K+ channels contribute to action potential repolarization and restrict the excitability of detrusor smooth muscle in the mouse bladder. In addition, the activation of voltage dependent K+ channels is involved in repolarization and after-hyperpolarization, and it has a fundamental role in stabilizing detrusor smooth muscle excitability.