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Action of imipramine on activated ATP-sensitive K(+) channels in interstitial cells of Cajal from murine small intestine

Cited 10 time in Web of Science Cited 10 time in Scopus
Authors
Choi, Seok; Park, Chan Guk; Kim, Man Yoo; Lim, Geon Han; Kim, Jin Ho; Yeum, Cheol Ho; Yoon, Pyung Jin; So, Insuk; Kim, Ki Whan; Jun, Jae Yeoul
Issue Date
2005-11-04
Publisher
Elsevier
Citation
Life Sci. 2006 Apr 11;78(20):2322-8. Epub 2005 Nov 2.
Keywords
ATP-Binding Cassette Transporters/*drug effectsAnimalsAntidepressive Agents, Tricyclic/*pharmacologyCells, CulturedEnzyme Inhibitors/pharmacologyFemaleGTP-Binding Proteins/antagonists & inhibitors/metabolismGastrointestinal Motility/drug effectsImipramine/*pharmacologyIntestine, Small/cytology/drug effects/*metabolismMaleMiceMice, Inbred BALB CPatch-Clamp TechniquesPinacidil/pharmacologyPotassium Channels, Inwardly Rectifying/*drug effectsProtein Kinase C/antagonists & inhibitors/metabolismVasodilator Agents/pharmacology
Abstract
Tricyclic antidepressants have been widely used for the treatment of depression and as a therapeutic agent for the altered gastrointestinal (GI) motility of irritable bowel syndrome (IBS). The aim of this study was to clarify whether antidepressants directly modulate pacemaker currents in cultured interstitial cells of Cajal (ICC). We used the whole-cell patch-clamp techniques at 30 degrees C in cultured ICC from the mouse small intestine. Treatment of pinacidil, an ATP-sensitive K(+) channel opener, in the ICC using the current clamping mode, produced hyperpolarization of the membrane potential and decreased the amplitude of the pacemaker potentials. With the voltage clamp mode, we observed a decrease in the frequency and amplitude of pacemaker currents and increases in the resting outward currents. These effects of pinacidil on pacemaker potentials and currents were completely suppressed by glibenclamide, an ATP-sensitive K(+) channel blocker. Also, with the current clamp mode, imipramine blocked the affect of pinacidil on the pacemaker potentials. Observations of the voltage clamp mode with imipramine, desipramine and amitryptyline suppressed the action of pinacidil in the ICC. Next, we examined whether protein kinase C (PKC) and the G protein are involved in the action of imipramine on pinacidil induced pacemaker current inhibition. We used chelerythrine, a potent PKC inhibitor and GDPbetaS, a nonhydrolyzable guanosine 5-diphosphate (GDP) analogue that permanently inactivates GTP-binding proteins. We found that pretreatment with chelerythrine and intracellular application of GDPbetaS had no influence on the blocking action of imipramine on inhibited pacemaker currents by pinacidil. We conclude that imipramine inhibited the activated ATP-sensitive K(+) channels in ICC. This action does not appear to be mediated through the G protein and protein kinase C. Furthermore, this study may suggest another possible mechanism for tricyclic antidepressants related modulation of GI motility.
ISSN
0024-3205 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16266721

http://hdl.handle.net/10371/24689
DOI
https://doi.org/10.1016/j.lfs.2005.09.032
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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