DESCRIPTION: Contractile function in ventricles surviving substantial myocardial infarction (MI) is improved by exercise training. The current proposal focuses on cellular mechanisms by which exercise training effects an improvement in contractile function. Our data demonstrate both altered (Ca2+)i dynamics in MI myocytes and exercise training enhance both Ca2+ influx and efflux pathways in normal myocytes. We hypothesize that exercise training can: (i) restore normal (Ca2+)i dynamics and contractile function to MI myocytes; and (ii) reverse MI-induced pathology in subcellular Ca2+ regulatory pathways. To test our hypothesis, male Sprague-Dawley rats will undergo LV infarct, allowed to recover for 3 weeks, studied with Echo to match LV infarct size (35-50 percent), and then start a 6-week high intensity sprint training (HIST). Single myocytes from the septum (remote from scar) and LV free wall (close to the scar) will be isolated from sedentary (Sed, MISed) and exercised-trained (HIST, MIHIST) rats. (Ca2+)i dynamics, contractile function and myosin heavy chain isoform distribution will be simultaneously measured with microfluorimetry, video edge detector and single cell SDS-PAGE. Ca2+ influx via L-type Ca2+ channel and Na+-Ca2+ exchange will be measured with whole-cell patch clamp. Releasable SR Ca2+ content will be assayed with caffeine induced SR Ca2+ release and rapid cooling contractures. SR Ca2+ uptake and SR Ca2+ leak will be examined. Finally, manipulations of Ca2+ fluxes will be undertaken to test the hypothesis that altered (Ca2+)i dynamics is causally related to depressed contraction function in MI myocytes and that HIST's beneficial effects on myocyte contractions are mediated via modulation of Ca2+ homeostatic pathways.
|Effective start/end date||7/1/98 → 1/31/14|
- National Institutes of Health: $416.00
- National Institutes of Health: $243,502.00
Myosin Heavy Chains
Sprague Dawley Rats
Polyacrylamide Gel Electrophoresis