Imipramine inhibits A-type delayed rectifier and ATP-sensitive K+ currents independent of G-protein and protein kinase C in murine proximal colonic myocytes
| Autor: | Seok Choi, Pyung Jin Yoon, Jin Ho Kim, Cheol Ho Yeum, Shankar P. Parajuli, Geon Han Lim, Jae Yeoul Jun |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Imipramine Patch-Clamp Techniques Colon G protein Myocytes Smooth Muscle In Vitro Techniques Pharmacology Membrane Potentials Glibenclamide Mice chemistry.chemical_compound KATP Channels GTP-Binding Proteins Drug Discovery Potassium Channel Blockers medicine Animals 4-Aminopyridine Enzyme Inhibitors Potassium Channels Inwardly Rectifying Protein kinase A Protein Kinase C Protein kinase C Mice Inbred BALB C Organic Chemistry Depolarization Chelerythrine chemistry Pinacidil Biophysics Molecular Medicine Female Delayed Rectifier Potassium Channels medicine.drug |
| Zdroj: | Archives of Pharmacal Research. 29:998-1005 |
| ISSN: | 1976-3786 0253-6269 |
| DOI: | 10.1007/bf02969284 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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