Ruthenium red as an effective blocker of calcium and sodium currents in guinea-pig isolated ventricular heart cells

Abstract

1. The effect of ruthenium red on calcium and sodium currents was studied in guinea-pig isolated ventricular heart cells with the whole cell patch-clamp technique.

2. Ruthenium red very efficiently blocked the L-type calcium current in a dose-dependent manner. A significant block was observed for concentrations as low as 0.3 μM. Analysis of the dose-response curve with the logistic equation indicated an EC₅₀ of 0.8 μM, a maximum inhibition of 85% reached at 5 μM, and a coefficient of 2.37.

3. There was no shift in the voltage-dependence of the Ca current activation, nor in that of its steady-state inactivation determined with a 1 s prepulse. However, removal of Ca current inactivation at positive voltage was considerably reduced in the presence of concentrations of ruthenium red above 1 μM. A slowing of the time-course of inactivation of the Ca current was also observed.

4. At 10 μM, a concentration generally used to block the sarcoplasmic Ca release channels or the mitochondrial Ca uptake, ruthenium red blocked 26.7±4.3% (n=8) of the sodium current, and slowed its inactivation time-course. No effect was observed on the voltage-dependence of the current activation or inactivation. The peak sodium current was also decreased at a 10 times lower concentration by 7.6±2.7% (n=3).

5. Thus, at concentrations used to assess intracellular Ca movements, ruthenium red induced in heart cells a significant block of both Ca and Na channels.

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