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Effects of MCC-135 on Ca2+ uptake by sarcoplasmic reticulum and myofilament sensitivity to Ca2+ in isolated ventricular muscles of rats with diabetic cardiomyopathy

  • Chapter
Biochemistry of Diabetes and Atherosclerosis

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 42))

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Abstract

Diabetic cardiomyopathy is characterized by delayed cardiac relaxation. Delayed relaxation is suggested to be associated with sarcoplasmic reticulum (SR) dysfunction and/or increase in myofilament sensitivity to Ca2+. Although MCC-135, an intracellular Ca2+-handling modulator, accelerates the delayed relaxation without inotropic effect in the ventricular muscle isolated from rats with diabetic cardiomyopathy, the underlying mechanism has not been fully understood. We tested the hypotheses that MCC-135 modulates Ca2+ uptake by SR and myofilament sensitivity to Ca2+. Wistar rats were made diabetic by a single injection of streptozotocin (40 mg/kg i.v.). Seven months later, the left ventricular papillary muscle was isolated and skinned fibers with and without functional SR were prepared by treatment of the papillary muscle with saponin to study SR Ca2+ uptake and myofilament sensitivity to Ca2+, respectively. In diabetic rats, SR Ca2+ uptake was decreased, which was related to decrease in protein level of SR Ca2+-ATPase determined by western blot analysis. MCC-135 enhanced SR Ca2+ uptake in diabetic rats, but not in normal rats. In diabetic rats, maximum force was decreased but force at diastolic level of Ca2+ was increased, without significant change in myofilament sensitivity to Ca2+ compared with normal rats. MCC-135 decreased force at any pCa tested (pCa 7.0-4.4), but had no significant effect on myofilament sensitivity to Ca2+ in diabetic rats. These results suggest that MCC-135 enhances SR Ca2+ uptake and shifts force-pCa curve downward without modulating myofilament sensitivity to Ca2+. These effects may contribute to positive lusitropic effect without inotropic effect of MCC-135 observed in the ventricular muscle of diabetic cardiomyopathy. (Mol Cell Biochem 249: 45–51, 2003)

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Authors and Affiliations

  1. Research Laboratory II, Cardiovascular Section, Mitsubishi Pharma Corporation, Aoba-ku, Yokohama, Japan

    Naoya Satoh & Yoshimi Kitada

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  1. Naoya Satoh
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  2. Yoshimi Kitada
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Editors and Affiliations

  1. Division of Stroke Vascular Disease, St. Boniface General Hospital Research Center, 351 Tache Avenue, R2H 2A6, Winnipeg, Manitoba, Canada

    James S. C. Gilchrist

  2. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Center, 351 Tache Avenue, R2H 2A6, Winnipeg, Manitoba, Canada

    Paramjit S. Tappia  & Thomas Netticadan  & 

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Satoh, N., Kitada, Y. (2003). Effects of MCC-135 on Ca2+ uptake by sarcoplasmic reticulum and myofilament sensitivity to Ca2+ in isolated ventricular muscles of rats with diabetic cardiomyopathy. In: Gilchrist, J.S.C., Tappia, P.S., Netticadan, T. (eds) Biochemistry of Diabetes and Atherosclerosis. Developments in Molecular and Cellular Biochemistry, vol 42. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9236-9_6

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  • DOI: https://doi.org/10.1007/978-1-4419-9236-9_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4852-8

  • Online ISBN: 978-1-4419-9236-9

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