Physiology

ELIZABETH SCHRODER STUMPF, Ph.D. Assistant Professor Ph.D. University of Buffalo, Roswell Park Division, 1995 Office: MS-510 Medical Center 0298 Tel: (859) 323-2918 E-mail: eschr0@uky.edu

Heart development proceeds because of reciprocal mechanical and functional processes. The molecular mechanisms and pathways responsible for linking mechanical to functional changes, however, are poorly understood. My recent work demonstrated that: 1) the developing heart responds in a region specific manner to altered mechanical load and that this response is mediated through cytoskeletal changes; and 2) the developing embryo expresses novel voltage-gated Ca²⁺ channels. These apparent theoretically disparate results are linked by our global hypothesis that: Embryonic ventricular myocytes translate cytoskeletal changes through a signaling complex to reciprocally regulate L-type Ca²⁺ channel current.  From cardiac and non-cardiac systems there are well-documented pathways of gene regulation via specific PM Ca²⁺ channels.  Electrophysiological data has demonstrated that the presence of both T and L type Ca²⁺ channels are dependent upon developmental age, species, and regional specificity. A major distinction between T- and L-type Ca²⁺ channels is that Ca_v3 channels do not require accessory subunits for ionic current expression. Because these channels functional requirements differ, the molecular characterization of PM Ca²⁺ channels and their accessory subunits is of critical importance in understanding their link to the cytoskeleton during both normal and altered development. In addition, the developmental gene program is recapitulated during adult heart disease. Therefore, information gained from studying development will provide insight into heart disease in the adult.

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