Endurance exercise training elicits improved cardiac contractile function and renders the heart more resistant to ischemic injury. The cellular adaptations that underlie these desirable central cardiac adaptations have not been clearly identified. There is evidence (mostly indirect) that altered myocardial transarcolemmal Ca2+ handling may be involved. Additionally, recent studies of intact LV cardiocytes provide evidence consistent with the idea that training increases the sensitivity of the contractile element (CE) to activation by Ca2+. These issues will be addressed using a female rat model of treadmill exercise training to accomplish the following Specific Aims.
Specific Aim 1 is to directly examine myocardial NaCa exchange activity in myocardium isolated from trained (TR) and sedentary (SED) rats. Fluorescence microscopy (fura-2), whole cell electrophysiology, and rapid solution switching techniques will be used to determine if training affects the voltage- and intracellular [Ca2+]-dependence of NaCa exchange currents (INaCa) and NaCa exchange-mediated explanations for the observations that training (i) increases the intropic sensitivity of the heart to extracellular [Ca2+] and [Na+] reduction and (ii) results in a smaller myocardial uptake of extracellular 45Ca2+ during bouts of ischemia.
Specific Aim 2 is to determine if training influences repolarizing K+ currents in a single cardiocytes using whole cell electrophysiological techniques. Time-dependent (I10) and time-independent (Is) K+ current densities and activation/inactivation characteristics will be determined. Alterations in these currents, particularly Ito, could affect ventricular action potential configuration and, therefore, transarcolemmal Ca2+ movement during excitation-contraction.
Specific Aim 3 is to directly determine if TR affects the sensitivity of the contractile element to activation by Ca2+ in intact cardiocytes and trabecular muscle preparations using fluorescence microscopy (fura-2), video edge detection, and isometric force transduction. This type of adaption has been inferred by studies of myocyte shortening and [Ca2+] dynamics and could provide an alternative explanation for the observation that training increases the inotropic sensitivity of the heart to altered extracellular [Na+] and [Ca2+] (see Specific Aim 1). Information resulting from this project will contribute to our understanding of the cellular processes that underlie the desirable adaptations of the heart to training and may be useful in the design of therapies that can be used in the treatment and prevention of heart disease.
Showing the most recent 10 out of 46 publications
