REGULATION OF BKCA CHANNELS DURING GESTATION

我目前是爱荷华大学生理学和生物物理系的终身教职助理教授。目前，我正处于事业发展的阶段，必须加强和促进我的研究计划，并以获得爱荷华大学的终身职位为长期目标。我的研究兴趣一直是钾通道在调节血管平滑肌和心肌细胞膜兴奋性方面的作用。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)在调节妊娠期间子宫平滑肌兴奋性和收缩能力中的作用。钾通道，由于其强大的缓冲细胞兴奋的能力，已被认为是一类潜在的宫缩治疗的靶点。这项建议的目的是确定BKCa通道剪接、变异表达或亚单位关联的调节是否与妊娠期间子宫兴奋性的功能差异相关。本研究的具体目的是：1)比较BKCa通道异构体在妊娠小鼠子宫平滑肌中的转录和蛋白表达模式；2)阐明BKCa通道β亚基在妊娠期间的转录和蛋白表达，并确定其与α亚基的组装在妊娠期间是否受到调节；3)确定BKCa通道剪接变异体在妊娠期间对子宫平滑肌收缩的调节作用；以及4)表征在雌激素和孕酮刺激下BKCa通道α亚基剪接变异体的表达。爱荷华大学为完成这种性质的研究提供了一个极好的环境。爱荷华大学医学院生理学和生物物理学系在离子通道调节、平滑肌功能和生殖内分泌学领域拥有成熟的互动研究人员。成功获得这一奖项后，我将能够将80%以上的精力投入到我的研究计划中，并通过阅读和参加这一领域的科学会议来熟悉生殖科学领域的文献、研究和研究人员。独立科学家奖将对我在爱荷华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.