The effect of flunarizine on intracellular calcium in isolated rat cardiomyocytes. A digital image processing study.
The molecular mechanisms associated with the effects of various pathological stimuli on myocardial tissue, as well as the mechanisms by which Ca2+ antagonists exert their protective effect, are poorly understood. With the use of digital image processing of Fura-2 fluorescence, we have shown that the mean intracellular free Ca2+ concentration of single isolated rat cardiomyocytes is increased upon exposure to various pathological stimuli (high extracellular Ca2+, veratrine). This increased Ca2+ content coincided with an increased number of hypercontracted cells. Pretreatment with flunarizine under these experimental conditions lowered the free intracellular Ca2+ concentration, thereby reducing the number of hypercontracted cells. Verapamil had no effect. The kinetics of changes in intracellular Ca2+ in electrically paced cardiomyocytes were not affected by flunarizine, but were significantly altered by the beta agonist isoprenaline. In addition, isoprenaline increased the mean diastolic intracellular free Ca2+ concentration of paced cardiomyocytes, whereas it remained unchanged in flunarizine treated cells. We conclude that flunarizine reduces intracellular free Ca2+ levels in isolated cardiomyocytes under pathological conditions, but does not affect physiological processes mediated by Ca2+. The report also illustrates the possibilities of digital imaging microscopy in the study of ion distributions in living cells.
Geerts
H
H
Janssen Research Foundation, Beerse, Belgium.
Nuydens
R
R
Nuyens
R
R
Ver Donck
L
L
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D003864:Depression, Chemical; D005444:Flunarizine / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives*; D006321:Heart / Q000187:drug effects*; D007091:Image Processing, Computer-Assisted; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D014700:Verapamil / Q000494:pharmacology; D014702:Veratrine / Q000494:pharmacology
D001572:Benzofurans; D005456:Fluorescent Dyes; C049925:fura-2-am; D014700:Verapamil; D014702:Veratrine; D007545:Isoproterenol; D005444:Flunarizine; D002118:Calcium; D016257:Fura-2