Alterations in contractile properties and Ca²⁺ handling in streptozotocin-induced diabetic rat myocardium

Abstract

The mechanisms of the slower time courses of Ca2+ transients (CaT) and contraction in diabetic (diabetes mellitus, DM) myocardium were studied. The aequorin method was applied to papillary muscles of streptozotocin-induced DM and control rats. The time courses of CaT and tension of twitch in DM were slower than those in control, although the magnitudes of the CaT and contraction were identical. The dependence of CaT decay time and relaxation time on developed tension in DM and control rats differed. The length-tension relation in twitch and the pCa-tension relation in tetanus were identical in the two groups. The magnitude of extra Ca2+ (transient increase in intracellular Ca2+ concentration induced by a quick release in tetanus) was identical in both groups. pCa-tension relations of skinned trabeculae at different sarcomere lengths were nearly identical. The cross-bridge cycling rate (CCR) in DM was slower than that in control. These results indicate that the tension-dependent change in the Ca2+ affinity of troponin C in DM myocardium functions as in control myocardium. The slower time courses of CaT and tension in DM myocardium are caused by slower Ca2+ uptake by the sarcoplasmic reticulum and the slower CCR.

Restoration of Cardiomyocyte Functional Properties by Angiotensin II Receptor Blockade in Diabetic Rats

“…In parallel, prolongation of APD, a major alteration in diabetic myocytes (29) attributable to a depressed I to (5,30), was also completely counteracted by losartan. Reversal of the AP prolongation might also have favorable effects on contractile function, especially relaxation, which is also severely prolonged in STZ-induced diabetic rats (31). Changing the driving rate from 0.2 to 1 Hz produced a statistically greater prolongation of APD in diabetic than in control cells, in agreement with previous experimental data (5) and a recent mathematical model of diabetesinduced electrophysiological alterations (30).…”

Superior Logistic Model for Decay of Ca2+ Transient and Isometric Relaxation Force Curve in Rabbit and Mouse Papillary Muscles

“…3,4) A linear relationship between Fτ E and Caτ E has been shown, even in low flow ischemia caused by graded reductions of coronary flow 5) and with inhibition of the SR Ca 2+ -ATPase with cyclopiazonic acid. 7) In contrast, there is no relationship between Fτ E and Caτ E in mild to moderate hypertrophic hearts.…”

“…However, the attachment of the CB influences the affinity of troponin (Tn) for [Ca 2+ ] i , which secondarily alters the relative timing and amplitude of the [Ca 2+ ] i decline and the relaxation force. 3,4) This feedback mechanism leads to a steeper or more cooperative force- [Ca 2+ ] i relationship, so that a given rise in systolic [Ca 2+ ] i produces a greater force than is evident in the absence of feedback.…”

Depressed Levels of Ca2+-Cycling Proteins May Underlie Sarcoplasmic Reticulum Dysfunction in the Diabetic Heart

“…Because the treatment of STZ-induced diabetic rats with insulin has been reported to prevent diabetes-induced changes in the heart (3)(4)(5)(6)(17)(18)(19)(20), it is likely that insulin deficiency may play a role in regulating cardiac protein content. Increased proteolysis shown to occur in the diabetic heart (34) is reduced by insulin (35).…”

“…iabetic cardiomyopathy has now been well documented in both clinical and experimental settings (1,2), and cardiac dysfunction in chronic diabetes has been linked to defective Ca 2ϩ -handling by cardiomyocytes (3,4). Although the sarcoplasmic reticulum (SR) Ca 2ϩ -pump and -release activities, which play a central role in regulating the intracellular level of Ca 2ϩ , are decreased in the diabetic heart (5,6), the mechanisms underlying these alterations are not fully understood.…”