Influence of experimental diabetes on sarcoplasmic reticulum function in rat ventricular muscle.
We examined whether the decrease in cardiac contractility in streptozotocin-induced diabetes in the rat is accompanied by reduced or excessive loading of the sarcoplasmic reticulum (SR) with Ca2+. Pooled SR Ca2+ content and fractional release on stimulation were estimated with rapid cooling contracture (RCC) and twitch height measurements, respectively. Interval-force relation was studied to assess the ability of diabetic tissue to alter the relative contribution of SR Ca2+ for contraction. Two months after injection with streptozotocin, peak isometric contraction and steady-state RCC decreased in parallel to approximately 50% of control values. The time to peak force development and complete relaxation was prolonged to 156 and 161% in diabetes in the presence of 1.25 and 2.5 mM extracellular Ca2+ concentration [Ca2+]o, respectively. A stepwise increase in the rate of stimulation from 0.2 to 0.5 and 1.0 Hz resulted in a negative force staircase, the slope of which was identical in control and diabetic animals in each [Ca2+]o tested. Postrest contractions and RCC, after variable test intervals, were significantly depressed after 0.2 and 0.5 Hz stimulation in diabetic muscles at 1.25 mM [Ca2+]o. This defect of SR Ca2+ availability was reversed by increasing the stimulation frequency to 1.0 Hz or by elevating [Ca2+]o to 2.5 mM. The results suggest that the marked reduction of developed tension in diabetic tissues was a consequence of depleted SR Ca2+ stores, rather than a result of chronic SR Ca2+ overloading. The maintained integrity of the interval-force relation in the presence of diabetes implies that the cellular mechanisms responsible for frequency- and time-dependent alterations in SR Ca2+ availability are not disturbed at this stage of disease.
Bouchard
R A
RA
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Bose
D
D
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003080:Cold Temperature; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles; D008297:Male; D009200:Myocardial Contraction; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D002118:Calcium