DEFECTIVE ALPHA, ADRENERGIC SIGNALING IN SENESCENT RAT

唐娜·H·科尔齐克博士是一名生理学家，目前由美国国立卫生研究院颁发的T32培训国家研究服务奖支持。科尔齐克博士一直致力于心脏收缩功能肾上腺素能调节领域的研究活动，因为它与慢性耐力运动和心脏病理生理学有关。KO1导师研究科学家发展奖将使她能够在过去研究经验的基础上发展，并补充她目前的研究技能，目的是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-第二信使偶联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具有不同背景和兴趣的个人的互动。该计划的一个独特方面包括与该应用程序相关的咨询导师团队。一个由知名研究人员组成的团队致力于科尔齐克博士在各自学科方面的指导和培训，并将在需要时进行直接互动。研究计划：在多种心脏疾病中，α1-肾上腺素能受体(α1-AR)系统在调节心脏收缩功能中起着重要的代偿作用。然而，对衰老心肌的观察表明，心脏对α1-AR刺激的变力反应是钝化的，而不是增强的，进一步削弱了衰老大鼠心室的功能储备能力。初步研究表明，这种反应可能是通过α1-AR信号转导通路中依赖PKC的臂的有效性减弱所介导的。其他Alpha1-AR信号级联组分的贡献尚不清楚。这项建议将系统地评估导致大鼠心脏α1-AR收缩功能障碍的α1-AR信号转导的细胞变化。研究还将探讨慢性运动在减轻α1-AR介导的收缩功能中与年龄相关的异常的作用和潜在机制。环境：密苏里大学的科尔齐克博士所处的环境是一个致力于研究和学术研究的环境，具有心血管科学的主要优势。

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.