title: Inhibition of pacemaker currents by nitric oxide via activation of ATP-sensitive K+ channels in cultured interstitial cells of Cajal from the mouse small intestine.
abstract: We investigated the role of nitric oxide (NO) in pacemaker activity and signal mechanisms in cultured interstitial cells of Cajal (ICC) of the mouse small intestine using whole cell patch-clamp techniques at 30 degrees C. ICC generated pacemaker potential in the current clamp mode and pacemaker currents at a holding potential of -70 mV. (+/-)-S-nitroso-N-acetylpenicillamine (SNAP; a NO donor) produced membrane hyperpolarization and inhibited the amplitude and frequency of the pacemaker currents, and increased resting currents in the outward direction. These effects were blocked by the use of glibenclamide (an ATP-sensitive K+ channel blocker), but not by the use of 5-hydroxydecanoic acid (a mitochondrial ATP-sensitive K+ channel blocker). Pretreatment with ODQ (a guanylate cyclase inhibitor) almost blocked the NO-induced effects. The use of cell-permeable 8-bromo-cyclic GMP also mimicked the action of SNAP. However, the use of KT-5823 (a protein kinase G inhibitor) did not block the NO-induced effects. Spontaneous [Ca2+]i oscillations in ICC were inhibited by the treatment of SNAP, as seen in recordings of intracellular Ca2+ ([Ca2+]i). These results suggest that NO inhibits pacemaker activity by the activation of ATP-sensitive K+ channels via a cyclic GMP dependent mechanism in ICC, and the activation of ATP-sensitive K+ channels mediates the inhibition of spontaneous [Ca2+]i oscillations.
authors.affiliation: Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, South Korea.
authors.forename: Chan Guk
authors.initials: CG
authors.lastname: Park
authors.forename: Young Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Man Yoo
authors.initials: MY
authors.lastname: Kim
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Cheol Ho
authors.initials: CH
authors.lastname: Yeum
authors.forename: Shankar Prasad
authors.initials: SP
authors.lastname: Parajuli
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Park
authors.forename: Han Seong
authors.initials: HS
authors.lastname: Jeong
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Ki Whan
authors.initials: KW
authors.lastname: Kim
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007421:Intestine, Small / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
chemical_list: D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D015221:Potassium Channels; D047428:Protein Kinase Inhibitors; C073601:KT 5823; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D005905:Glyburide; D002118:Calcium