Altered calcium handling in compensated hypertrophied rat cardiomyocytes induced by pressure overload.
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.
Sumida
E
E
Third Department of Medicine, Kurume University School of Medicine, Japan.
Nohara
M
M
Muro
A
A
Sumida
E
E
Kaku
H
H
Koga
Y
Y
Toshima
H
H
Imaizumi
T
T
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured / Q000166:cytology; D005576:Colforsin / Q000494:pharmacology; D006321:Heart / Q000033:anatomy & histology; D006439:Hemodynamics; D006706:Homeostasis; D006973:Hypertension / Q000150:complications*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D000318:Adrenergic beta-Agonists; D005576:Colforsin; D007545:Isoproterenol; D002118:Calcium