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Altered calcium handling in compensated hypertrophied rat cardiomyocytes induced by pressure overload
1Third Department of Medicine, Kurume University School of Medicine, Japan.
Insights
Compensated hypertrophied cardiomyocytes show increased calcium transients (Ca-Amp) and reduced myofilament responsiveness. This adaptive response in cardiac function may involve altered beta-adrenergic signaling pathways.
Area of Science:
- Cardiology
- Cell Physiology
- Biochemistry
Background:
- Cardiac hypertrophy, a thickening of the heart muscle, can lead to heart failure.
- Understanding calcium (Ca2+) handling is crucial for comprehending cardiomyocyte function during compensated hypertrophy.
Purpose of the Study:
- To investigate Ca2+ handling and contraction in compensated hypertrophied rat cardiomyocytes.
- To explore the adaptive mechanisms and beta-adrenergic responses in these cells.
Main Methods:
- Induction of compensated hypertrophy via aortic constriction (AC) in rat models.
- Simultaneous measurement of Ca2+ transients (using indo-1/AM fluorescence) and myocyte contraction (circumferential length).
- Assessment of responses to pharmacological agents like isoproterenol and forskolin.
Main Results:
- Hypertrophied cardiomyocytes exhibited a higher Ca2+ transient amplitude (Ca-Amp) compared to controls.
- A positive correlation between Ca-Amp and fractional shortening (FS) was observed, but the FS/Ca-Amp ratio was lower in AC rats.
- While both groups responded to forskolin, AC myocytes showed reduced responsiveness to isoproterenol, suggesting altered beta-adrenergic signaling.
Conclusions:
- Compensated hypertrophied cardiomyocytes display an adaptive increase in Ca-Amp with reduced myofilament Ca2+ responsiveness.
- The observed alterations in beta-adrenergic response are likely due to changes in beta-adrenoceptor number, G-protein function, or coupling.
Abstract:
To investigate Ca2+ handling in compensated hypertrophied cardiomyocytes, we measured Ca2+ transients and contraction of hypertrophied rat left ventricular myocytes induced by aortic constriction (AC). The fluorescence ratio (I405/I480) after indo-1/AM loading and circumferential length were simultaneously measured in isolated myocytes. The amplitude of Ca2+ transients (Ca-Amp) was higher in rats with AC than in sham-operated rats (Sham) (0.25 +/- 0.08 vs 0.17 +/- 0.05). There was a positive correlation between Ca-Amp and fractional shortening (FS) in both AC and Sham rats, whereas the ratio of FS/Ca-Amp was smaller in AC rats. These observations suggest that compensated hypertrophied cardiomyocytes exhibit an adaptive increase in Ca-Amp, associated with reduced myofilament responsiveness to an increase in Ca2+. Isoproterenol and forskolin increased Ca-Amp and FS, and decreased time to 50% decline of Ca2+ transients. Although myocytes from AC rats exhibited reduced responsiveness to isoproterenol, responses to forskolin did not differ between the 2 groups. The reduced beta-adrenergic response in Ca2+ handling was probably due to altered beta-adrenoceptor numbers, G-protein function and/or their coupling process.