title: INaCa and ICl(Ca) contribute to isoproterenol-induced delayed after depolarizations in midmyocardial cells.
abstract: The contributions of electrogenic sodium/calcium exchange current (INaCa), calcium-activated chloride conductance [ICl(Ca)], and calcium-activated nonselective cation conductance to delayed afterdepolarizations (DAD) were examined. Nonselective cation channels were absent in canine M cells, since inhibition of INaCa and ICl(Ca) eliminated all calcium-activated currents without abolishing cell shortening. After the cells were treated with isoproterenol and ouabain to increase calcium loading, INaCa was 168 +/- 30 x 10(-3) pC/pF and ICl(Ca) was 114 +/- 24 x 10(-3) pC/pF. Transient overlapping inward and outward currents were evoked positive to the chloride reversal potential (ECl). Outward current was chloride sensitive, and inward current was blocked by replacement of external sodium with lithium. When ECl was -50 mV, triggered activity occurred in normal external sodium and persisted after inhibition of INaCa. Steps to -80 mV revealed oscillating inward currents in normal sodium and chloride, which persisted after inhibition of INaCa. When ECl was equal to -113 mV, ICl(Ca) opposed INaCa at the resting potential. DAD occurred in normal sodium, and inhibition of outward ICl(Ca) provoked triggered activity. We conclude that INaCa represents approximately 60% of the total calcium-activated current at resting potentials but that both INaCa and ICl(Ca) work in concert to cause DAD in calcium-overloaded cells.
authors.affiliation: Department of Experimental Cardiology, Masonic Medical Research Laboratory, Utica, New York 13501, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Zygmunt
authors.forename: R J
authors.initials: RJ
authors.lastname: Goodrow
authors.forename: C M
authors.initials: CM
authors.lastname: Weigel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism; D002712:Chlorides / Q000502:physiology*; D004285:Dogs; D004553:Electric Conductivity; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007473:Ion Channels / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011930:Reaction Time / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D002412:Cations; D002712:Chlorides; D007473:Ion Channels; D019831:Sodium-Calcium Exchanger; D010042:Ouabain; D007545:Isoproterenol; D002118:Calcium