THE ALPHA-1C CALCIUM CHANNEL IN MUSCLE

描述(改编自申请人摘要)：L型电压门控 钙通道也被称为二氢吡啶受体(Dhprs)是至关重要的。 用于骨骼肌和心肌的兴奋-收缩偶联。每个人 在这些肌肉类型中，表达其自身的DHPR亚型。美国政府的角色 毫无疑问，心肌中的Alpha1C心脏DHPR既提供了 也需要钙离子的流入来触发细胞内钙离子的释放 以便提供一种手段，在这些商店耗尽时重新填充它们。在……里面 血管平滑肌这些相同的通道是几乎所有 钙通道阻滞剂在高血压和高血压治疗中的应用 心脏病。最近，某些成人骨骼肌被证明可以 不仅表现出DHPR的α1S骨架异构体，而且还表现出α1C 心脏异构体，尽管表达水平较低。这笔拨款是对 心肌DHPR在成人骨骼肌中作用的几种假说。 将被测试的假设包括重新填充部分耗尽的 细胞内钙储存，预防疲劳，并用于关闭其他 基因。方法将包括张力、(钙)i和电生理测量。 以及基因表达的测量。这一结果可能会暗示更多的角色 对于心脏以及许多平滑肌肉中的Alpha1C心脏DHPR。 这笔赠款还试图确定类固醇激素地塞米松是如何 蛋白激酶C抑制剂星状孢子素和电刺激的调节 心肌脱氢表雄酮受体在肌肉中的表达及其反应 参与转录因子和组织特异性转录因子的元件 在基因启动子中的表达。其他方法将包括 用于启动子的传统检测方法是有效的。这些结果将增强 对这个极其重要的转录调控的理解 高血压和心脏治疗中的治疗药物受体 疾病。

DESCRIPTION (Adapted from the applicant's abstract): L-type voltage-gated calcium channels also known as dihydropyridine receptors (DHPRs) are critical for excitation-contraction coupling in both skeletal and cardiac muscle. Each of these muscle types expresses its own isoform of the DHPR. The role of the alpha1C cardiac DHPR in cardiac muscle is unquestionable to both provide the influx of Ca2+ needed to trigger Ca2+ release from intracellular stores as well as to provide a means to refill those stores when they become depleted. In vascular smooth muscle these same channels are the site of action of nearly all Ca2+ channel blockers used therapeutically in the treatment of hypertension and heart disease. Recently certain adult skeletal muscles have been shown to exhibit not only the alpha1S skeletal isoform of the DHPR, but also the alpha1C cardiac isoform, although at lower levels of expression. This grant tests several hypotheses for the role of the cardiac DHPR in adult skeletal muscle. The hypotheses to be tested include refilling of partially depleted intracellular Ca2+ stores, forestalling fatigue, and serving to turn off other genes. Methods will include tension, (Ca2+)i and electrophysiology measurements and measurements of gene expression. The results may suggest additional roles for the alpha1C cardiac DHPRs in the heart as well as in many smooth muscles. This grant also seeks to determine how the steroid hormone dexamethasone, the protein kinase C inhibitor staurosporine, and electrical stimulation regulate the expression of the cardiac DHPR in muscle, and to determine the response elements for the transcription factors involved and for tissue-specific expression within the gene promoter. Additional methods will include traditional assays used for promoter work. These results will enhance understanding of the transcriptional regulation of this extremely important receptor for therapeutic agents in the treatment of hypertension and heart disease.