Modulation of slow waves by hyperpolarization with potassium channel openers in antral smooth muscle of the guinea-pig stomach.
Modulation of spontaneous electrical activities (slow waves, pacemaker potentials and follower potentials) in response to hyperpolarization produced by the ATP-sensitive K+ channel openers (KCOs) pinacidil or nicorandil was investigated in smooth muscle tissues of the guinea-pig stomach antrum. With hyperpolarization, the amplitude of slow waves and follower potentials was reduced and that of pacemaker potentials was increased, with a minor modulation of their frequency. The attenuation of slow waves was associated with an inhibition of the 1st component and abolition of the 2nd component. All these actions of KCOs were antagonized by glibenclamide. An increase in the extracellular K+ concentration prevented the KCO-induced hyperpolarization with partial restoration of slow waves, suggesting that the inhibition was produced mainly by a decrease in membrane resistance. Exposure of tissues to KCOs for a long period of time (> 20 min) resulted in the reappearance of slow waves displaying both 1st and 2nd components. The 2nd component of the slow wave, which displayed a slower recovery, was inhibited again by 5-hydroxydecanoic acid, an inhibitor of mitochondrial ATP-sensitive K+ channels. Noradrenaline hyperpolarized the membrane by activating apamin-sensitive K+ channels and increased the amplitude and frequency of slow waves through activation of alpha 1-adrenoceptors, actions different from those of KCOs. Thus, inhibition of slow waves by KCOs may be primarily related to the decrease in amplitude of a passive electrotonic component, possibly due to a reduction of the input resistance. The hyperpolarization shifted the threshold potential for generation of the 2nd component of slow waves to negative levels, presumably due to modulation of mitochondrial functions.
Kito
Yoshihiko
Y
Department of Physiology, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan.
Suzuki
Hikaru
H
D018528:ATP-Binding Cassette Transporters; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D020108:Nicorandil / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists* / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011706:Pyloric Antrum / Q000187:drug effects / Q000502:physiology; D013270:Stomach / Q000187:drug effects
D018528:ATP-Binding Cassette Transporters; D000316:Adrenergic alpha-Agonists; D003652:Decanoic Acids; D006880:Hydroxy Acids; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D020108:Nicorandil; C052853:5-hydroxydecanoic acid; D020110:Pinacidil; D005905:Glyburide; D009638:Norepinephrine