소장 향도잡이 세포의 전기적 활동도에 대한 산화질소의 효과

Abstract

To investigate the role of nitric oxide (NO) on the pacemaker activity and the signal mechanism in cultured interstitial cells of Cajal (ICC) of mouse small intestine whole cell patch-clamp techniques performed at 30℃. ICC generated slow waves in current clamp mode (I=0) and pacemaker currents at a holding potential of -70 mV in voltage clamping mode. (±)-S-nitroso-N-acetylpenicillamine (SNAP; a NO donor) produced the membrane hyperpolarization and inhibited the amplitude and frequency of pacemaker currents and increased resting currents in the outward direction. These effects were blocked by glibenclamide (an ATP-sensitive K+channel blocker), but not 5-hydroxydecanoic acid (5-HD; a mitochondrial ATP-sensitive K+ channel blocker). ATP-sensitive K+channels openers showed the mimicked action with SNAP and antagonized by glibenclamide. Pretreatment of ODQ (a guanylate cyclase inhibitor) almost blocked the NO-induced effects. Also, a cell permeable 8-bromo-cyclic GMP showed the mimicked action with SNAP. However, KT-5823 (a protein kinase G inhibitor) did not block the NO-induced effects. These results suggest that NO inhibits pacemaker activity by the activation of ATP-sensitive K+ channels via cyclic GMP dependent mechanism in intestinal ICC