It is well known that endurance exercise training elicits uniformly favorable adaptations in myocardial performance. Training is known to alter the configuration of the ventricular action potential (AP) and the inotropic responsiveness of heart to changes in extracellular (Ca2+) and (Na+). To date, however, the cellular basis for these adaptations has not been clearly identified. In the last funding period of this project, we have identified training adaptations in both the transient (Ito) and sustained (Is) components of the composite, outward repolarizing K+ current in rat left ventricular (LV) cardiocytes. These repolarizing K+ currents play a central role in defining AP configuration, and may well be the cellular basis for the effect of training on AP characteristics. Recently, composite Ito and Ito currents have been resolved into at least 4 other discrete outward currents. In addition, some of these discrete currents and the K+ channel proteins that are thought to be responsible for those currents are known to be differentially distributed across specific regions of the LV. In this project, Specific Aim 1 is to determine the effect of training on the specific current components that contribute to the composite Ito and Isus in rat LV using whole cell, electrophysiological techniques.
Specific Aim 2 is to determine whether or not the effects of training on the specific currents that contribute to the composite transient and sustained currents are regionally distributed in the heart. Finally, we recently acquired intriguing preliminary evidence for a subtle training-induced decrease in intracellular Ca2+ buffering capacity. This type of adaptation could provide a cellular explanation for the consensus observation that training alters the inotropic responsiveness of heart to changes in extracellular (Ca2+) and (Na+).
Specific Aim 3 is to use electrophysiological techniques and more refined fluorescence microscopic techniques to confirm or refute this potentially important finding. Exercise training is known to be effective in the prevention and treatment of wide variety cardio pathologic conditions. Elucidation of the cellular changes that underlie these positive adaptations may be of particular importance in the design, development, and implementation of molecular and pharmacological heart disease treatment and prevention strategies. This is particularly significant in view of the fact that heart disease claims more North American lives than any other disease.
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