Depressed cardiac tension cost in experimental diabetes is due to altered myosin heavy chain isoform expression.
Cardiac disease in diabetes presents as impaired left ventricular contraction and relaxation; however, the mechanisms underlying contractile protein dysfunction during the progression of disease are unknown. Accordingly, we assessed Ca(2+)-dependent tension development and tension-dependent ATP consumption (tension cost) in a rat model early (6 wk) and late (12 wk) after the onset of diabetes (50 mg/kg iv streptozotocin) using mechanical force- and enzyme-coupled UV absorbance measurements. Myofilament Ca(2+) sensitivity and maximal tension were unchanged between groups at either time point. Cross-bridge cycling rate was significantly decreased in diabetes, as indexed by tension cost (early control 5.4 +/- 0.4 and early diabetes 4.2 +/- 0.3; and late control 6.0 +/- 0.2 and late diabetes 4.2 +/- 0.2; P < 0.05). Because rodent models of cardiac disease are confounded by altered myosin isoform distribution, myosin content was determined by SDS-PAGE and densitometry. The cardiac content of alpha-myosin in diabetes was decreased to 41% +/- 4.1 at 6 wk and 32.5% +/- 2.9 at 12 wk of diabetes (early control 77.8% +/- 3.3 and late control 73.6% +/- 2.5). Separate control experiments demonstrated a linear decrease in tension cost with decreased alpha-myosin content. Given this, the depression of tension cost in this rodent model of diabetes could be fully explained by the altered myosin isoform distribution.
Center for Cardiovascular Research, Department of Physiology, University of Illinois at Chicago, 835 S. Wolcott (M/C 901 Chicago, IL 60612, USA.
Veronica L M
VL
Rundell
David L
DL
Geenen
Peter M
PM
Buttrick
Pieter P
PP
de Tombe
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction; D018995:Myosin Heavy Chains / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D024723:Ventricular Myosins / Q000378:metabolism*
D024723:Ventricular Myosins; D018995:Myosin Heavy Chains