REGULATION OF BKCA CHANNELS DURING GESTATION

我目前是爱荷华州大学生理学和生物物理学系的终身助理教授。 目前，我在我的职业发展阶段，这是必不可少的，以加强和促进我的研究计划与获得在爱荷华州大学终身职位的长期目标。 我的研究兴趣是钾通道在调节血管平滑肌和心肌细胞膜兴奋性中的作用。 最近，我冒险进入生殖生理学研究领域，研究大电导钙激活钾通道（BKCa）在妊娠期调节子宫平滑肌兴奋性和收缩性中的作用。 钾通道由于其有效缓冲细胞兴奋的能力，已被建议作为宫缩抑制治疗的一类潜在靶点。 本建议的目的是确定是否BKCa通道剪接变异体的表达或亚基协会的调制相关的功能差异，在妊娠期子宫兴奋性。 这项建议的具体目标是：1）比较妊娠期间小鼠子宫平滑肌中BKCa通道亚型的转录物和蛋白质表达模式，2）阐明妊娠期间BKCa通道β亚基转录物和蛋白质表达，并确定其与α亚基的组装是否在妊娠期间受到调节，3）确定BKCa通道剪接变体对妊娠期间子宫平滑肌收缩调节的贡献，和4）表征用雌激素和孕酮刺激后BKCa通道α亚基的剪接变体的表达。 爱荷华州大学提供了一个很好的环境来完成这种性质的研究。 生理学和生物物理学系和爱荷华州大学医学院在离子通道调节、平滑肌功能和生殖内分泌学领域拥有完善的互动研究人员。 成功获得该奖项后，我将能够将80%以上的精力投入到我的研究计划中，并通过阅读和参加该领域的科学会议来熟悉生殖科学领域的文献，研究和调查人员。独立科学家奖将对促进我在爱荷华州大学的职业发展产生重大影响。

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.