마우스 대장 운동성 조절에 있어 항우울제의 효과

Abstract

ABSTRACT

Effects of Antidepressive Agents on the Modulation of Colonic Motility in Mouse

Oh Hyun Jung Advisor: Prof, Sang Hoon Kim M.D. Ph.D. Department of Medicine, Graduate School of Chosun University

Tricyclic antidepressants were beneficial to not only depression but also functional gastrointestinal motility disorders. This study was investigated to the antidepressants effects on spontaneous pacemaker activities of cultured colonic interstitial cells of Cajal (ICC) from mouse using whole-cell patch clamp technique in 30oC, RT-PCR and Ca2+-imaging. Colonic ICC generated spontaneous periodic pacemaker potentials in currents-clamping mode. The pacemaker potentials were not modified by tetrodotoxin (a voltage-dependent Na+ channels blocker), nicardipine (a voltage-dependent Ca2+ channels blocker), or tetraethylammonium (a voltage-dependent K+ channels blocker). However, glibenclamide (an ATP-sensitive K+ channels blocker) depolarized the resting membrane and increased frequency of pacemaker potentials. Exposure of imipramine also depolarized the membrane and increased frequency of pacemaker potentials. Pinacidil, an opener of ATP-sensitive K+ channels, hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Pinacidil-induced effects were recovered to normal by glibenclamide or imipramine. However, 5-hydroxydecanoic acid, a mitochondrial ATP-sensitive K+ channels blocker, had no effects on pacemaker potentials. In RT-PCR analysis, c-kit positive ICC expressed Kir 6.1 and SUR 2B subunits of ATP sensitive K+ channels. In recording of intracellular Ca2+ concentrations using Fluo-4, imipramine or glibenclamide increased the Ca2+ oscillations. These results suggested that imipramine suppressed the basally activated ATP sensitive K+ channels that are related intracellular Ca2+ oscillations. Therefore, it seems that imipramine may useful to improve the altered colonic motility, especially in decreased motility disorders.

Keywords: imipramine, colon, interstitial cells of Cajal, pacemaker potentials, ATP-sensitive K+ channels.