This proposal is a request for a Mentored Research Scientist Development Award (KO1) that would allow the applicant to establish the following career objectives: (1) develop her expertise in cardiovascular research, which is new to the candidate (2) continue her training in calcium experiments as well as master new skills in electrophysiology (3) develop an independent research program in alcohol research. The Department of Pathology, Anatomy and Cell Biology is committed to in the etiology of alcohol-related diseases, and has been awarded an Alcohol Research Center. The investigators are concerned with the effects of alcohol at the cellular, subcellular and molecular level, and employ a wide range of experimental techniques for these studies. The candidate will be in an ideal environment to develop her scientific career in association with personnel committed to providing mentored support for young scientists in the field of alcohol research. As the focus for establishing her long-term research career in alcohol and heart research, the candidate and preceptor have jointly designed the following research proposal that combines her past technical training with newly established skills and plans for future training in cardiac physiology. Long term alcohol exposure has adverse effects on cardiac tissue. This includes alteration in cardiac contractile functions and reduced responsiveness to catecholamines. In this research plan, an animal model USA alcohol-fed Fischer rats will be employed that has previously been demonstrated to develop alcohol- induced cardiopathologies similar to those found in human alcoholics. Chronic ethanol-induced lesions will be studied at the cellular level using individual ventricular myocytes. Changes in contractility and beta-adrenergic responsiveness due to long-term ethanol exposure will be examined using a high speed digital imaging system and a laser scanning confocal microscope; these systems have been developed in the preceptor's laboratory for similar experiments. Preliminary results from this laboratory demonstrate that chronic ethanol reduces beta- adrenergic enhancement of excitation-contraction coupling and sarcolemmal calcium channel activity. Continuing experiments with single cell imaging, electrophysiology and molecular biology are planned to further characterize the mechanisms responsible for alterations in catecholamine effects on alcohol-impaired myocytes.
| Solem, M; Almas, J; Rubin, E et al. (2000) Changes in activity and regulation of the cardiac Ca2+ channel (L-type) by protein kinase C in chronic alcohol-exposed rats. Alcohol Clin Exp Res 24:1145-52 |
| Pecherskaya, A; Solem, M (2000) IGF1 activates PKC alpha-dependent protein synthesis in adult rat cardiomyocytes. Mol Cell Biol Res Commun 4:166-71 |
| Solem, M L; Thomas, A P (1998) Modulation of cardiac Ca2+ channels by IGF1. Biochem Biophys Res Commun 252:151-5 |
