Imipramine inhibits A-type delayed rectifier and ATP-sensitive K+ currents independent of G-protein and protein kinase C in murine proximal colonic myocytes.
The effects of imipramine on A-type delayed rectifier K+ currents and ATP-sensitive K+ (KATP) 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 K+ 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 K+ currents was reduced by external application of imipramine. The half-inactivation potential and the half-recovery time of A-type delayed rectifier K+ currents were not changed by imipramine. With 0.1 mM ATP and 140 mM K+ in the pipette and 90 mM K+ in the bath solution and a holding potential of -80 mV, pinacidil activated inward currents; this effect was blocked by glibenclamide. Imipramine also inhibited KATP currents. The inhibitory effects of imipramine in A-type delayed rectifier K+ currents and KATP currents were not changed by guanosine 5-O-(2-thiodiphosphate) (GDPbetaS) and chelerythrine, a protein kinase C inhibitor. These results suggest that imipramine inhibits A-type delayed rectifier K+ currents and KATP currents in a manner independent of G-protein and protein kinase C.
Choi
Seok
S
Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Parajuli
Shankar Prasad
SP
Lim
Geon Han
GH
Kim
Jin Ho
JH
Yeum
Cheol Ho
CH
Yoon
Pyung Jin
PJ
Jun
Jae Yeoul
JY
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D054086:KATP Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*
D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D015761:4-Aminopyridine; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D007099:Imipramine