title: Ionic basis for the regulation of spontaneous excitation in detrusor smooth muscle cells of the guinea-pig urinary bladder.
abstract: (1) The regulatory mechanisms of spontaneous excitation in detrusor smooth muscles of the guinea-pig urinary bladder were investigated using intracellular microelectrode and muscle tension recording techniques. (2) Detrusor smooth muscle cells exhibited nifedipine-sensitive spontaneous action potentials. Their frequency was highly sensitive to membrane polarization and was reduced by lowering the temperature. Lowering the temperature also reduced the frequency of spontaneous contractions and increased their amplitude. (3) Charybdotoxin (50 nm) and iberiotoxin (0.1 microm) increased the amplitude and duration of action potentials, and abolished after hyperpolarizations (AHPs). Both agents also increased the amplitude and duration of spontaneous contractions, and reduced their frequency. Apamin (0.1 microm) did not change the shape of action potentials but often converted individual action potentials into bursts. It also increased the amplitude and duration of spontaneous contractions, and reduced their frequency. 4-aminopyrideine (4-AP, 1 mm) increased the frequency of action potentials without affecting their shape, and increased the amplitude and frequency of spontaneous contractions. (4) Cyclopiazonic acid (CPA, 10 microm) and ryanodine (50 microm) increased the amplitude of action potentials, and suppressed AHPs. Both agents also increased the amplitude and duration of spontaneous contractions, and reduced their frequency. 1,2-(Bis (2-aminophenoxy) ethane-N,N,N', N'-tetraacetic acid tetrakis (acetoxymethyl ester) (50 microm) dramatically increased the amplitude and duration of the action potential, and abolished AHPs. (5) Spontaneous action potentials in detrusor smooth muscles cells result from the opening of L-type Ca2+ channels, and their frequency is regulated by voltage-dependent mechanisms and by some metabolic process. Both the activation of large conductance Ca2+-activated K+ (BK) channels and Ca2+-mediated inactivation of the Ca2+ channels are involved in the repolarizing phase of action potentials. The Ca2+ influx through L-type Ca2+ channels triggers calcium-induced calcium release via ryanodine receptors and activates BK channels to generate AHPs. Both small conductance Ca2+-activated K+ channels and voltage-sensitive K+ channels may contribute to the resting membrane potential and regulate the frequency of action potentials. The regulatory mechanisms of action potentials are closely related to the regulation of spontaneous contractions.
authors.affiliation: University Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK. hikaru.hashitani@pharmacology.ox.ac.uk
authors.forename: Hikaru
authors.initials: H
authors.lastname: Hashitani
authors.forename: Alison F
authors.initials: AF
authors.lastname: Brading
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; D007473:Ion Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C064719:iberiotoxin