Ca2+-activated non-selective cation current in rabbit ventricular myocytes.
Oscillatory currents (OCs) were studied in isolated rabbit ventricular myocytes with whole cell mode voltage clamp using Na+-free intracellular and extracellular solutions under conditions where K+ currents were anticipated to be eliminated or minimized. All OCs were dependent on release of Ca2+ from the sarcoplasmic reticulum (SR) because they were associated with intracellular Ca2+ ([Ca2+]i) transients, and were suppressed by high concentrations of BAPTA (20 mmol l-1) or pretreatment with the SR antagonist agents ryanodine (10 micromol l-1) or thapsigargin (1 micromol l-1). The reversal potential (Vrev) for OCs shifted with changes in the calculated Vrev for Cl- (ECl) but was between ECl and the calculated Vrev for elemental monovalent cations (ECat), indicating that more than one Ca2+-activated current contributed to OCs. Addition of the Ca2+-activated Cl- current (ICl(Ca)) antagonist, niflumic acid, shifted the OC Vrev to ECat, suggesting that ICl(Ca) and a Ca2+-activated non-selective cation current (ICAN) contributed to the observed OCs. A reduced niflumic acid-insensitive Ca2+-activated OC persisted following marked symmetrical reduction of Cl- in the intracellular and extracellular solutions. Subsequent removal of all extracellular monovalent cations, by N-methyl-D-glucamine (NMDG) substitution, eliminated OCs and the inward holding current suggesting that ICAN and ICl(Ca) accounted for all or most of the Ca2+-activated OC in the absence of Na+. The OC Vrev was equal to ECl in the absence of monovalent elemental cations. Under these conditions niflumic acid eliminated all OCs. Macroscopic OC is partially due to ICAN in rabbit ventricular myocytes.
Wu
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The Cardiac Arrhythmia Section, Division of Cardiovascular Medicine, Department of Internal Medicine, Vanderbilt University Medical School, Nashville, TN 37232-6300, USA.
Anderson
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D000818:Animals; D002118:Calcium / Q000502:physiology*; D002414:Cations, Monovalent / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D007425:Intracellular Membranes / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009991:Oscillometry; D011817:Rabbits; D016276:Ventricular Function
D002414:Cations, Monovalent; D002712:Chlorides; D002118:Calcium