Diabetes rapidly induces contractile dysfunctions in isolated ventricular myocytes.
To determine whether diabetes-induced cardiac dysfunction is due to contractile dysfunction at the single-cell level, mechanical properties and Ca2+ transients were evaluated in ventricular myocytes isolated from diabetic rats. Rats were made diabetic by injection with streptozotocin and killed either 4-6 days or 8 wk after treatment. Shortening and relengthening (twitch) properties were evaluated in isolated myocytes with a high-resolution (120-Hz) video-based edge-detection system during electrical stimulation between 0.1 and 5 Hz. A separate cohort of myocytes was loaded with fura 2 to assess intracellular Ga2+ transients. Long-term (8-wk) but not short-term (4- to 6-day) diabetes depressed peak twitch amplitude. Diabetes markedly prolonged both the contraction and relaxation phases from both diabetic models. Additionally, 35% of the long-term diabetic myocytes could not pace at 5 Hz, and 48% of the short-term diabetic myocytes developed a hypercontracture at that frequency. Intracellular Ca2+ measurements showed slower Ca(2+)-transient decays in myocytes from short-term diabetic rats. These data demonstrate that contractile dysfunction seen in the diabetic heart is due, in part, to abnormalities of the myocyte. Furthermore, these abnormalities are present after only 4-6 days of diabetes, suggesting a rapid alteration in the processes regulating myocyte shortening and relengthening, which likely include impaired Ca2+ sequestration or extrusion.
Ren
J
J
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Davidoff
A J
AJ
D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016276:Ventricular Function
D002118:Calcium