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Experimental Diabetes Research
Volume 2012 (2012), Article ID 829758, 11 pages
Research Article

Ca+2/Calmodulin-Dependent Protein Kinase Mediates Glucose Toxicity-Induced Cardiomyocyte Contractile Dysfunction

1Department of Geriatrics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
2Department of Physiology, The Fourth Military Medical University, Xi'an 710032, China
3Division of Pharmaceutical Sciences, University of Wyoming, College of Health Sciences, Laramie, WY 82071, USA

Received 22 March 2012; Accepted 29 March 2012

Academic Editor: Yingmei Zhang

Copyright © 2012 Rong-Huai Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


(1) Hyperglycemia leads to cytotoxicity in the heart. Although several theories are postulated for glucose toxicity-induced cardiomyocyte dysfunction, the precise mechanism still remains unclear. (2) This study was designed to evaluate the impact of elevated extracellular Ca2+ on glucose toxicity-induced cardiac contractile and intracellular Ca2+ anomalies as well as the mechanism(s) involved with a focus on Ca2+/calmodulin (CaM)-dependent kinase. Isolated adult rat cardiomyocytes were maintained in normal (NG, 5.5 mM) or high glucose (HG, 25.5 mM) media for 6-12 hours. Contractile indices were measured including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time-to-PS (TPS), and time-to-90% relengthening (TR90). (3) Cardiomyocytes maintained with HG displayed abnormal mechanical function including reduced PS, ±dL/dt, and prolonged TPS, TR90 and intracellular Ca2+ clearance. Expression of intracellular Ca2+ regulatory proteins including SERCA2a, phospholamban and Na+-Ca2+ exchanger were unaffected whereas SERCA activity was inhibited by HG. Interestingly, the HG-induced mechanical anomalies were abolished by elevated extracellular Ca2+ (from 1.0 to 2.7 mM). Interestingly, the high extracellular Ca2+-induced beneficial effect against HG was abolished by the CaM kinase inhibitor KN93. (4) These data suggest that elevated extracellular Ca2+ protects against glucose toxicity-induced cardiomyocyte contractile defects through a mechanism associated with CaM kinase.