REGULATION OF BKCA CHANNELS DURING GESTATION

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I am currently a tenure-track Assistant Professor in the Department of Physiology and Biophysics at the University of Iowa. Presently, I am at a stage of my career development where it is essential to enhance and foster my research program with the long-term goal of obtaining a tenured position at the University of Iowa. My research interest has been in the role of potassium channels in regulating vascular smooth muscle and cardiac myocyte membrane excitability. Recently, I have ventured into the reproductive physiology research area to investigate the role of the large-conductance calcium-activated potassium channel (BKCa) in modulating uterine smooth muscle excitability and contractility during gestation. Potassium channels, due to their ability to potently buffer cell excitation, have been suggested as one potential class of targets for tocolytic therapy. The objective of this proposal is to determine whether modulation of BKCa channel splice variant expression or subunit association correlates to a functional difference in uterine excitability during gestation. The specific aims of this proposal are to: 1) compare transcript and protein expression patterns of BKCa channel isoforms in mouse uterine smooth muscle during gestation, 2) elucidate BKCa channel beta subunit transcript and protein expression during gestation and detemine whether its assembly with the alpha subunit is modulated during pregnancy, 3) determine the contribution of BKCa channel splice variants to the regulation of uterine smooth muscle contraction during gestation, and 4) characterize the expression of the splice variants of the BKCa channel alpha subunit following stimulation with estrogen and progesterone. The University of Iowa provides an excellent environment to complete studies of this nature. The Department of Physiology and Biophysics and University of Iowa College of Medicine has well-established interactive investigators in the fields of ion channel regulation, smooth muscle function, and reproductive endocrinology. With successful attainment of this award, I would be able to devote greater than 80 percent to my research program and familiarizing myself with the literature, research, and investigators in the reproductive sciences field through reading and attending scientific meetings in this area. An Independent Scientist Award will have a major impact in promoting my career development at the University of Iowa.