Subcellular calcium content in cardiomyopathic hamster hearts in vivo: an electron probe study.
In the Syrian cardiomyopathic hamster heart, abnormal cellular calcium regulation, resulting in cellular calcium overload, is believed to play a role in the pathogenesis of cardiac hypertrophy and failure. Alternatively, the primary abnormality may be coronary vasospasm, resulting in reperfusion-induced necrosis. According to the latter hypothesis, only those cells that suffer an ischemic insult would contain elevated calcium levels. To determine whether a generalized elevation in myocytic calcium exists in myopathic hamster hearts, we measured cellular and subcellular calcium concentrations by electron probe microanalysis in cryosections of 50-day and 96-day myopathic and control hearts, rapidly frozen in vivo. Total calcium content of ventricular homogenates from each group was also measured by atomic absorption spectrophotometry. No significant differences in subcellular calcium were found by electron probe microanalysis among 50-day and 96-day myopathics and their age-matched controls. In 50-day myopathic and control hearts, mitochondrial calcium was 0.7 +/- 0.2 and 0.9 +/- 0.2, respectively, and A-band calcium was 3.0 +/- 0.4 and 2.6 +/- 0.4 mmol calcium/kg dry wt(+/- SEM). Results from 96-day animals were similar. Localized regions of elevated calcium were found only at sites of necrotic foci: in Na+-loaded cells (mitochondria: 4.7 +/- 1.3 (SEM) mmol/kg dry wt), in dying cells (mitochondria: 72 +/- 22 (SEM) mmol/kg dry wt) or as extracellular deposits (7-10 mol/kg dry wt). Total calcium content of hearts from myopathic hamsters, as determined by atomic absorption spectrophotometry, was also 13 times (50-day) and 50 times (96-day) higher than controls. These results demonstrate that there is a marked heterogeneity in cellular calcium content in myopathic hamster hearts, but the data do not support the hypothesis of a generalized cellular calcium overload.
Bond
M
M
Department of Heart and Hypertension, Research Institute of the Cleveland Clinic Foundation, OH 44195-5069.
Jaraki
A R
AR
Disch
C H
CH
Healy
B P
BP
D000818:Animals; D002118:Calcium / Q000032:analysis*; D009202:Cardiomyopathies / Q000378:metabolism*; D006224:Cricetinae; D004577:Electron Probe Microanalysis; D005629:Frozen Sections; D008929:Mitochondria, Heart / Q000032:analysis; D009206:Myocardium / Q000032:analysis*; D013054:Spectrophotometry, Atomic; D013347:Subcellular Fractions / Q000032:analysis*
D002118:Calcium