ALTERATIONS IN SARCOPLASMIC-RETICULUM CALCIUM-STORING PROTEINS IN PRESSURE-OVERLOAD CARDIAC-HYPERTROPHY

The alterations of intracellular calcium (Ca2+) homeostasis may be res ponsible for the contractile defects in pressure-overload cardiac hype rtrophy. The Ca2+-adenosinetriphosphatase (ATPase) protein level of th e sarcoplasmic reticulum (SR) is reduced in the hypertrophied or faili ng heart. However, it is not known whether Ca2+-storing proteins, incl uding calsequestrin and calreticulin, are also altered during cardiac hypertrophy. We quantified SR Ca2+-regulatory proteins using Western b lot analysis in left ventricular (LV) muscle isolated from sham-operat ed control rats (n = 6) and rats with pressure overload 4 wk after abd ominal aortic constriction (n = 7). The contractile function of isolat ed LV myocytes, assessed by the sarcomere motion measured with laser d iffraction, was depressed in aortic-constricted rats. The SR Ca2+-ATPa se protein level was decreased to 56 +/- 9% (SE) of the control value in hypertrophied myocardium (P < 0.01). The calsequestrin protein leve l was not altered, whereas calreticulin was increased by 120 +/- 3% of the control value in aortic-constricted rats (P < 0.05). The alterati ons in SR Ca2+-regulatory proteins were equally observed in hypertroph ied hearts even when the results were normalized using the amounts of myosin heavy chain proteins in each sample. Immunohistochemical staini ng of calsequestrin in the control heart showed cross striations at th e Z Lines, whereas calreticulin was hardly observed within myocytes bu t was intense within interstitial fibroblasts. In the hypertrophied he art, calreticulin was observed at the perinuclear region within the my ocyte cytoplasm. These data indicate that pressure-overload cardiac hy pertrophy causes the alterations in SR Ca2+-storing proteins as well a s in Ca2+-ATPase, which may contribute to the contractile dysfunction of the hypertrophied myocytes.