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Ca 2+ ‐activated non‐selective cation current in rabbit ventricular myocytes
Author(s) -
Wu Yuejin,
Anderson Mark E.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.0051m.x
Subject(s) - niflumic acid , chemistry , extracellular , thapsigargin , bapta , intracellular , divalent , antagonist , biophysics , ryanodine receptor , inorganic chemistry , stereochemistry , biochemistry , receptor , biology , organic chemistry
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 Ca 2+ from the sarcoplasmic reticulum (SR) because they were associated with intracellular Ca 2+ ([Ca 2+ ] i ) transients, and were suppressed by high concentrations of BAPTA (20 mmol l −1 ) or pretreatment with the SR antagonist agents ryanodine (10 μmol l −1 ) or thapsigargin (1 μmol l −1 ). 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 Ca 2+ ‐activated current contributed to OCs. Addition of the Ca 2+ ‐activated Cl − current ( I Cl(Ca) ) antagonist, niflumic acid, shifted the OC V rev to E Cat , suggesting that I Cl(Ca) and a Ca 2+ ‐activated non‐selective cation current ( I CAN ) contributed to the observed OCs. A reduced niflumic acid‐insensitive Ca 2+ ‐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 Ca 2+ ‐activated OC in the absence of Na + . The OC V rev was equal to E Cl in the absence of monovalent elemental cations. Under these conditions niflumic acid eliminated all OCs. Macroscopic OC is partially due to I CAN in rabbit ventricular myocytes.