Transient Ca2+ overload alters Ca2+ handling in rat cardiomyocytes: effects on shortening and relaxation.
Transient Ca2+ overload in cardiomyocytes occurs during pathophysiological conditions. The aim of the present study was to investigate the effects of transient Ca2+ overload on shortening and relaxation in isolated rat cardiomyocytes electrically stimulated at 0.5 Hz and to examine whether transient Ca2+ overload induces alterations in Ca2+ handling and myofilament sensitivity. Fractional shortening and shortening velocity fell to 79 +/- 5% (P < 0.05) and 78 +/- 4% (P < 0.01) 2 min after exposure to high Ca2+. A transient decrease in resting length, a reduction in relaxation velocity to 86 +/- 7% (P < 0.05), and a prolonged time of relaxation with 8.3 +/- 4.3% (P < 0.05) were also observed. Systolic fluorescence ratio using fura 2 as the Ca2+ indicator fell by 11.0%, and the decline of the fluorescence ratio was prolonged by 29.8%. By applying caffeine, we observed a significant reduction in sarcoplasmic reticulum Ca2+ content after transient Ca2+ overload. A significant reduction in myofilament sensitivity was also observed. In conclusion, the systolic dysfunction observed after transient Ca2+ overload is the result of both decreased systolic Ca2+ and reduced myofilament sensitivity. The relaxation abnormalities are most likely caused by altered Ca2+ handling, since we observed a reduction in the sarcoplasmic reticulum Ca2+ content and a prolongation of the decline of the fura 2 transient.
Holt
E
E
Institute for Experimental Medical Research, University of Oslo, Norway. even.holt@ioka.uio.no
Christensen
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009210:Myofibrils / Q000502:physiology; D009994:Osmolar Concentration; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D002118:Calcium