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.
Rundell
Veronica L M
VL
Center for Cardiovascular Research, Department of Physiology, University of Illinois at Chicago, 835 S. Wolcott (M/C 901 Chicago, IL 60612, USA.
Geenen
David L
DL
Buttrick
Peter M
PM
de Tombe
Pieter P
PP
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