S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Physiology (생리학교실) Journal Papers (저널논문_생리학교실)
Phentolamine Inhibits the Pacemaker Activity of Mouse Interstitial Cells of Cajal by Activating ATP-Sensitive K(+) Channels
- Ahn, Seung Whan; Kim, Sang Hun; Choi, Seok; Kim, Jin Ho; Yeum, Cheol Ho; Sun, Jae Myeong; Jun, Jae Yeoul; So, Insuk; Wie, Hee Wook
- Issue Date
- PHARMACEUTICAL SOC KOREA
- ARCHIVES OF PHARMACAL RESEARCH; Vol.33 3; 479-489
- Interstitial cells of Cajal; Pacemaker activities; ATP-sensitive K(+) channels; Phentolamine
- The aim of this study was to clarify if phentolamine has proven effects on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine involving the ATP-sensitive K(+) channels and adrenergic receptor. The actions of phentolamine on pacemaker activities were investigated using whole-cell patch-clamp technique and intracellular Ca(2+) analysis at 30 degrees C in cultured mouse intestinal ICC. ICC generated spontaneous pacemaker currents at a holding potential of -70 mV. Treatment with phentolamine reduced the frequency and amplitude of the pacemaker currents and increased the resting outward currents. Moreover, under current clamping (I = 0), phentolamine hyperpolarized the ICC membrane and decreased the amplitude of the pacemaker potentials. We also observed that phentolamine inhibited spontaneous [Ca(2+)](i) oscillations in ICC. The alpha-adrenergic drugs prazosin, yohimbine, methoxamine, and clonidine had no effect on ICC intestinal pacemaker activity and did not block phentolamine-induced effects. Phentolamine-induced effects on the pacemaker currents and the pacemaker potentials were significantly inhibited by ATP sensitive K(+) channel blocker glibenclamide, but not by TEA, apamin, or 4-aminopyridine. In addition, the NO synthase inhibitor, L-NAME and the guanylate cyclase inhibitor, ODQ were incapable of blocking the phentolamine-induced effects. These results demonstrate that phentolamine regulates the pacemaker activity of ICC via ATP-sensitive K(+) channel activation. Phentolamine could act through an adrenergic receptor- and also through NO-independent mechanism that involves intracellular Ca(2+) signaling.
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