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KMID : 0043320060290110998
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Archives of Pharmacal Research
2006 Volume.29 No. 11 p.998 ~ p.1005
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Imipramine Inhibits A-type Delayed Rectifier and ATP-Sensitive K+ Currents Independent of G-Protein and Protein Kinase C in Murine Proximal Colonic Myocytes
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Choi Seok
Parajuli Shankar Prasad
Lim Geon-Han
Kim Jin-Ho
Yeum Cheol-Ho
Yoon Pyung-Jin
Jun Jae-Yeoul
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Abstract
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The effects of imipramine on A-type delayed rectifier currents and ATP-sensitive currents were studied in isolated murine proximal colonic myocytes using the whole-cell patch-clamp technique. Depolarizing test pulses between-80 mV and +30 mV with 10 mV increments from the holding potential of-80 mV activated voltage-dependent outward currents that peaked within 50 ms followed by slow decreasing sustained currents. Early peak currents were inhibited by the application of 4-aminopyridine, whereas sustained currents were inhibited by the application of TEA. The peak amplitude of A-type delayed rectifier currents was reduced by external application of imipramine. The half-inactivation potential and the half-recovery time of A-type delayed rectifier currents were not changed by imipramine. With 0.1 mM ATP and 140 mM in the pipette and 90 mM in the bath solution and a holding potential of -80 mV, pinacidil activated inward currents; this effect was blocked by glibenclamide. Imipramine also inhibited currents. The inhibitory effects of imipramine in A-type delayed rectifier currents and currents were not changed by guanosine 5-O-(2-thiodiphosphate) () and chelerythrine, a protein kinase C inhibitor. These results suggest that imipramine inhibits A-type delayed rectifier currents and currents in a manner independent of G-protein and protein kinase C.
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KEYWORD
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A-type delayed rectifier currents, ATP-sensitive currents, Imipramine, Colonic myocytes
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