© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Sodium influx via a non-selective pathway activated by the removal of extracellular divalent cations: possible role in the calcium paradox
aInterdisciplinair Research Centrum, KUL Campus Kortrijk, University of Leuven, Leuven, Belgium
bCentrum voor Experimentele Heelkunde en Anesthesiologie, University of Leuven, Leuven, Belgium
* Corresponding author. Tel.: +32-16-347-132; fax: +32-1634-7139 kanigula.mubagwa{at}kuleuven.ac.be
Objective: Cation non-selective conductances which are induced upon removal of extracellular divalent cations have been identified in cardiac and other cells. We have examined whether the conductance identified in cardiac myocytes mediates an increase in intracellular Na+ (Nai+) and have tested the ability of drugs to prevent this influx. Methods: Rat single ventricular myocytes at 22°C were voltage-clamped in whole-cell mode to measure membrane currents or were loaded with SBFI to measure Nai+. Results: Removal of extracellular Ca2+ (Cao2+) and Mg2+ (Mgo2+), which induced a current with reversal potential of –10 mV, also caused an increase in SBFI fluorescence ratio (340/380 nm). These changes were reversible on repletion of Cao2+ and/or Mgo2+. They could not be prevented by nifedipine, indicating that they were not mediated by L-type Ca2+ channels. Both increases in non-selective conductance and in Nai+ were prevented by trivalent cations (Dyo3+, Gdo3+ or Lao3+; 100 µM) or reduced by the aminoglycoside gentamicin. Conclusion: A cation non-selective conductance, different from L-type Ca2+ channels, contributes to the Nai+ accumulation obtained during perfusion with Ca2+/Mg2+-free media, hence also to the Cai2+ overload and cellular damage upon Cao2+ repletion (the Ca2+ paradox).
KEYWORDS Experimental; Heart; Electrophysiology; Pathophysiology; Myocytes; Intra/extracellular ions; Ion transport; Membrane currents; Intracellular sodium; Calcium paradox
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