Ca2+-activated non-selective cation current in rabbit ventricular myocytes

1. 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. 2. 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 mu mol l(-1)) or thapsigargin (1 mu mol l(-1)). 3. The reversal potential (V-rev) for OCs shifted with changes in the calculated V-rev for Cl- (E-Cl) but was between E-Cl and the calculated V-rev for elemental monovalent cations (E-Cat), indicating that more than one Ca2+-activated current contributed to OCs. 4. Addition of the Ca2+-activated Cl- current (I-Cl(Ca)) antagonist, niflumic acid, shifted the OC V-rev to E-Cat, suggesting that I-Cl(Ca) and a Ca2+-activated non-selective cation current (I-CAN) contributed to the observed OCs. 5. 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 I-CAN and I-Cl(Ca) accounted for all or most of the Ca2+-activated OC in the absence of Na+. 6. The OC V-rev was equal to E-Cl in the absence of monovalent elemental cations. Under these conditions niflumic acid eliminated all OCs. 7. Macroscopic OC is partially due to I-CAN in rabbit ventricular myocytes.