Biophys J, September 2000, p. 1273-1284, Vol. 79, No. 3

Inhibition of Ca²⁺ Sparks by Ruthenium Red in Permeabilized Rat Ventricular Myocytes

Valeriy Lukyanenko,^* Inna Györke,^* Saisunder Subramanian, Anton Smirnov,^* Theodore F. Wiesner, and Sandor Györke^*

 ^*Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, and  Department of Chemical Engineering, Texas Tech University, Lubbock, Texas 79409-3121 USA

We have compared the effects of the sarcoplasmic reticulum (SR) Ca²⁺ release inhibitor, ruthenium red (RR), on single ryanodine receptor (RyR) channels in lipid bilayers, and on Ca²⁺ sparks in permeabilized rat ventricular myocytes. Ruthenium red at 5 µM inhibited the open probability (P_o) of RyRs ~20-50-fold, without significantly affecting the conductance or mean open time of the channel. At the same concentration, RR inhibited the frequency of Ca²⁺ sparks in permeabilized myocytes by ~10-fold, and reduced the amplitude of large amplitude events (with most probable localization on the line scan) by ~3-fold. According to our theoretical simulations, performed with a numerical model of Ca²⁺ spark formation, this reduction in Ca²⁺ spark amplitude corresponds to an ~4-fold decrease in Ca²⁺ release flux underlying Ca²⁺ sparks. Ruthenium red (5 µM) increased the SR Ca²⁺ content by ~2-fold (from 151 to 312 µmol/l cytosol). Considering the degree of inhibition of local Ca²⁺ release events, the increase in SR Ca²⁺ load by RR, and the lack of effects of RR on single RyR open time and conductance, we have estimated that Ca²⁺ sparks under normal conditions are generated by openings of at least 10 single RyRs.

Biophys J, September 2000, p. 1273-1284, Vol. 79, No. 3
© 2000 by the Biophysical Society   0006-3495/00/09/1273/12  $2.00

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