Oximes: 'enzymatic' slow channel antagonists in canine cardiac purkinje fibers?
In mammalian cardiac muscle voltage-dependent activation of slow channels, e.g., the slow inward current channel, may be possible only when the channels are phosphorylated. We examined the electrophysiological actions of oximes, mile nucleophilic agents which show 'phosphatase-like' activity in isolated enzyme systems, to assess their actions on slow channels in cardiac Purkinje fibers. Diacetyl monoxime (DAM) and pyridine-2-aldoxime (NorPAM) produced a marked, reversible and concentration-dependent reduction in the action potential (AP) plateau duration and abolished spontaneous phase 4 depolarization, but produced only minimal effects on resting potential, dV/dt max, action potential amplitude, duration of phase 3, or membrane resistance. Slow response action potentials evoked in the presence of elevated potassium plus isoproterenol or in Na-free solution were abolished by DAM. The effects of DAM on the AP plateau were antagonized by epinephrine, but an increase in Ca was relatively ineffective. The results suggest that oximes may act as surrogate phosphatases to remove phosphate groups which regulate the availability of slow current channels for voltage-dependent activation.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors; D002586:Cesium / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D010091:Oximes / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000494:pharmacology*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology
D007473:Ion Channels; D010091:Oximes; D002586:Cesium; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium; D004837:Epinephrine