REGULATION OF CARDIAC ION CHANNEL EXPRESSION

描述(改编自申请人的摘要)：申请人 假设生理和药物刺激导致 电压门控性钾钙通道基因表达的变化 这反过来会改变心脏中心肌细胞的兴奋性。生化的， 提出了免疫组织化学和电生理实验。 检验以下假设：1)地塞米松调节心肌细胞 动作电位上电压门控性K~+和Ca~(2+)电流 地塞米松诱导通道mRNAs和细胞表面增加 心肌细胞中的通道蛋白，对于Kv1.5，这将是 3)地塞米松作用于间盘 直接作用于培养的成年心肌细胞改变通道基因 表达；以及4)改变单个KV1亚基的合成可以 影响多种同聚体和/或异构体钾的表达 频道。这些研究将确定是否激素控制K+和 钙离子通道表达是一种新的长期调控机制 心脏的兴奋性。

DESCRIPTION (adapted from the applicant's abstract): The applicant hypothesizes that physiological and pharmacological stimuli induce changes in voltage-gated potassium and calcium channel gene expression that in turn alter myocyte excitability in the heart. Biochemical, immunohistochemical, and electrophysiological experiments are proposed to test hypotheses that; 1) dexamethasone regulates cardiomyocyte voltage-gated K+ and Ca2+ currents in action potentials; 2) dexamethasone induces increases in channel mRNAs and cell-surface channel proteins in cardiomyocytes and in the case of Kv1.5 this will be evident as an increase at the intercalated disc; 3) dexamethasone acts directly on cultured adult cardiomyocytes to alter channel gene expression; and 4) altering the synthesis of a single Kv1 subunit can affect the expression of multiple homomeric and/or heteromeric potassium channels. These studies will determine if hormonal control of K+ and Ca2+ channel expression is a novel mechanism for long-term regulation of cardiac excitability.