title: Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder.
abstract: The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM). A higher concentration of NS1619 (30μM) hyperpolarized the membrane and abolished action potential firing. NS309 (10μM) and SKA31 (100μM), small conductance Ca(2+)-activated K(+) (SK) channel openers, dramatically increased the duration of the after-hyperpolarization and then abolished action potential firing in an apamin (100nM)-sensitive manner. Flupirtine (10μM), a Kv7 channel opener, inhibited action potential firing without hyperpolarizing the membrane in a manner sensitive to XE991 (10μM), a Kv7 channel blocker. BRL37344 (10μM), a β3-adrenceptor agonist, or rolipram (10nM), a phosphodiesterase 4 inhibitor, also inhibited action potential firing. A higher concentration of rolipram (100nM) hyperpolarized the DSM and abolished the action potentials. IbTX (100nM) prevented the rolipram-induced blockade of action potentials but not the hyperpolarization. BK and Kv7 channels appear to predominantly contribute to the stabilization of DSM excitability. Spare SK channels could be pharmacologically activated to suppress DSM excitability. BK channels appear to be involved in the cyclic AMP-induced inhibition of action potentials but not the membrane hyperpolarization.
authors.affiliation: Departmentof Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Departmentof Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. Electronic address: hasitani@med.nagoya-cu.ac.jp.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Hashitani
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D015640:Ion Channel Gating / Q000187:drug effects*; D051656:KCNQ Potassium Channels / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D001562:Benzimidazoles; D051656:KCNQ Potassium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; C086491:NS 1619; D000242:Cyclic AMP
keywords: BK channel; Cyclic AMP; Detrusor smooth muscle; Kv7 channel; SK channel; Urinary bladder