Diminished expression of sarcoplasmic reticulum Ca2+-ATPase and ryanodine sensitive Ca2+ channel mRNA in streptozotocin-induced diabetic rat heart

The diabetic heart has an abnormal intracellular calcium ([Ca2+]i) metabolism. However, the responsible molecular mechanisms are unclear. The present study aimed to investigate mRNAs expressed in the proteins which regulate heart [Ca2+]i metabolism in streptozotocin (STZ)-induced diabetic rats. Expression of sarcoplasmic reticulum Ca2+-adenosine triphosphatase (SR Ca2+-ATPase) mRNA was significantly less in the heart 3 weeks after STZ injection than that in the age-matched controls. Together with the down-regulation of SR Ca2+-ATPase, expression of ryanodine sensitive Ca2+ channel (RYR) mRNA was also decreased 12 weeks after STZ injection. Insulin supplementation fully restored the decreased mRNAs expression of SR Ca2+-ATPase and RYR. The diminished expression and restoration with insulin supplementation of SR Ca2+-ATPase was further confirmed at the protein level. In contrast, expression of mRNAs coding the L-type Ca2+ channel, Na+-Ca2+ exchanger, or phospholamban were not affected 3 or 12 weeks after STZ injection. These results can be taken to indicate that the down-regulation of SR Ca2+-ATPase and RYR mRNAs is a possible underlying cause of cardiac dysfunction in STZ-induced diabetic rats. (C) 2000 Academic Press.