Cyclosporine increases the intracellular free calcium concentration in electrically paced isolated rat cardiomyocytes.
The effect of cyclosporine on the mean cytoplasmic free calcium concentration in electrically paced single cardiomyocytes from adult rats was studied. Cardiac myocytes were paced by electrical field stimulation with either 2 or 3 Hz in the presence of 5 micrograms/ml cyclosporine or the solvent cremophor. Exposure to cyclosporine during 40 minutes of electrical 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 concentration was measured by means of digital image processing of fura-2 fluorescence. Electrical field stimulation increased the cytoplasmic free calcium from 69.7 +/- 5.4 to 124.9 +/- 24.5 nmol/L Ca2+ in the presence of the solvent and from 84.2 +/- 25.4 to 250.1 +/- 55.9 nmol/L in the presence of cyclosporine (p = 0.036 versus solvent). The data provide direct 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.
Olbrich
H G
HG
Abteilung für Kardiologie, Universität Frankfurt am Main, Federal Republic of Germany.
Donck
L V
LV
Geerts
H
H
Mutschler
E
E
Kober
G
G
Kaltenbach
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000494:pharmacology; D013997:Time Factors
D012997:Solvents; C022131:cremophor; D011092:Polyethylene Glycols; D016572:Cyclosporine; D002118:Calcium