DEFECTIVE ALPHA, ADRENERGIC SIGNALING IN SENESCENT RAT

Donna H. Korzick博士是一名生理学家，目前得到了美国国立卫生研究院T32培训国家研究服务奖的支持。Korzick博士在心脏收缩功能的肾上腺素能调节领域的研究活动中表现出了重大的承诺，因为它与慢性耐力运动和心脏病理生理学有关。KO1指导研究科学家发展奖将使她能够在过去的研究经验的基础上，补充她目前的研究技能，在心血管衰老领域建立一个独立的研究生涯。职业发展/培训计划：本奖项期间概述的培训活动包括特别强调在受体-第二信使耦合领域获得大量分子和生化技术。参加药理学，生理学和兽医生物医学科学的研讨会将促进与不同背景和兴趣的个人的互动。该计划的一个独特之处包括与此应用程序相关的咨询导师团队。一组著名的研究人员致力于Korzick博士的指导和培训，他们各自的学科和直接的互动将在需要时发生。研究计划：最近提出了alpha1-肾上腺素能受体（alpha1-AR）系统在各种心脏病理中调节心脏收缩功能的重要代偿作用。然而，对衰老心肌的观察表明，心脏对α 1- ar刺激的肌力反应减弱而不是增强，进一步降低了衰老大鼠心室的功能储备能力。初步研究表明，这种反应可能是由α - 1- ar信号转导通路中pkc依赖臂的有效性降低所介导的。其他α 1- ar信号级联成分的作用尚不清楚。本研究将系统评估大鼠心脏α 1- ar信号转导的细胞变化对α 1- ar收缩功能障碍的影响。研究还将探讨慢性运动在减弱α - 1- ar介导的收缩功能的年龄相关畸变中的作用及其潜在机制。环境：密苏里大学Korzick博士周围的环境以致力于心血管科学的研究和学术奖学金为标志。

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.