CYCLOSPORINE INCREASES THE INTRACELLULAR FREE CALCIUM-CONCENTRATION IN ELECTRICALLY PACED ISOLATED RAT CARDIOMYOCYTES

The effect of cyclosporine on the mean cytoplasmic free calcium concen tration in electrically paced single cardiomyocytes from adult rats wa s studied. Cardiac myocytes were paced by electrical field stimulation with either 2 or 3 Hz in the presence of 5 mug/ml cyclosporine or the solvent cremophor. Exposure to cyclosporine during 40 minutes of elec trical pacing caused irreversible hypercontracture in most cells, only 22.1% +/- 1.2% (mean +/- SEM) remained rod-shaped versus 64.1% +/- 3. 2% in the solvent (p = 0.01). The cytoplasmic free calcium concentrati on was measured by means of digital image processing of fura-2 fluores cence. Electrical field stimulation increased the cytoplasmic free cal cium from 69.7 +/- 5.4 to 124.9 +/- 24.5 nmol/L Ca2+ in the presence o f the solvent and from 84.2 +/- 25.4 to 250.1 +/- 55.9 nmol/L in the p resence of cyclosporine (p = 0.036 versus solvent). The data provide d irect evidence that cyclosporine enhances the cytoplasmic free calcium concentration in single paced rat cardiomyocytes. These findings may be of importance in the consideration of a possible cardiotoxicity of cyclosporine.