Regulation of Na⁺, K⁺ATPase Isoenzymes; Gender differences in myocardial aging

One of the research interests in our laboratory is to study the various aspects of transmembrane ion transport in cardiac and skeletal muscle cells. Currently, our research is focused on elucidating the cellular and molecular mechanisms regulating multiple gene families of the Na⁺, K⁺-ATPase, the functional unit of the Na pump. We are investigating how different physiological conditions, such as postnatal development and exercise training, such as cardiac hypertrophy and heart failure, alter expression and function of these isoforms in myocardium. In addition, we are investigating regulation and function of the Na-pump in aging skeletal muscle. Na-K pump maintains Na/K homeostasis, and thus modulates contractile function of skeletal muscle. Significant changes in expression of the Na⁺, K⁺-ATPase isozymes occur in skeletal muscle of aging rats. The goal of this study is to determine whether aging is associated with deficits in expression and function of the Na-K pump and in K⁺-balance, and whether physical activity attenuates/reverses these deficits. The long term goal is to delineaste mechanisms underlying age-related loss of muscle function.

Another research interest of this laboratory is to elucidate mechanisms underlying gender-related differences in myocardial aging. Clinical and epidemiological studies clearly demonstrate that men and women differ in adaptation of their myocardium to various physiological and pathological modulations. The short-term goal is to confirm and establish that the aging F344/BN rat is a relevant and unique model for studying gender differences in myocardial aging, and to begin elucidating the underlying mechanisms. These studies may help identify cellular targets responsible for gender-specific adaptation of the aged heart and help facilitate development of better gender-specific strategies in diagnosis and treatment of heart failure in the elderly. The ultimate goal is to develop interventions, which may be gender specific, that may delay or reverse myocardial aging.