DEFECTIVE ALPHA, ADRENERGIC SIGNALING IN SENESCENT RAT

点击翻译按钮获取中文摘要

Donna H. Korzick, Ph.D. is a physiologist currently supported by a T32 Training National Research Service Award from NIH. Dr. Korzick has demonstrated significant commitment to research activities in the area of adrenergic regulation of cardiac contractile function as it pertains to chronic endurance exercise and cardiac pathophysiology. The KO1 Mentored Research Scientist Development Award would enable her to build upon past research experiences and compliment her current research skills with the intent of establishing an independent reseach career in the field of cardiovascular aging. Career Development/Training Plan: The training activities outlined for the duration of this award include a particular emphasis on acquisition of a significant number of molecular and biochemical techniques in the area of receptor-second messenger coupling. Attendance of seminars in pharmacology, physiology and veterinary biomedical sciences will foster interactions with individuals with diverse backgrounds and interests. A unique aspect of this plan includes the team of consulting mentors associated with this application. A team of renowned investigators are committed to Dr. Korzick's mentoring and training with regard to their respective disciplines and direct interactions will occur as needed. Research Plan: An important compensatory role for the alpha1-adrenergic receptor (alpha1-AR) system in regulating cardiac contractile function in a variety of cardiac pathologies has recently been proposed. Observations from senescent myocardium, however, suggest the inotropic responsiveness of the heart to alpha1-AR stimulation is blunted rather than enhanced, further diminishing the functional reserve capacity of the aging rat ventricle. Preliminary studies suggest that this response may be mediated by diminished effectiveness of the PKC-dependent arm of the alpha1-AR signal transduction pathway. The contribution of other alpha1-AR signaling cascade components are unknown. This proposal will systematically evaluate cellular changes in alpha1-AR signal transduction responsible for alpha1-AR contractile dysfunction in rat heart. Studies will also address the role of chronic exercise in attenuating age-related aberrations in alpha1-AR mediated contractile function and underlying mechanisms. Environment: The environment surrounding Dr. Korzick at the University of Missouri is one marked by a commitment to research and academic scholarship with major strengths in cardiovascular sciences.