CA CHANNELS, CHARGE MOVEMENT & MYOPLASMIC CA TRANSIENTS

CA 通道，电荷运动

• 批准号: 3159010
• 负责人: ENRICO STEFANI
• 金额: $ 15.61万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3159010
• 关键词: Anura; action potentials; alpha adrenergic agent; beta adrenergic agent; calcium channel; calcium metabolism; cell differentiation; cell membrane; cyclic AMP; denervation; drug metabolism; laboratory rat; muscle cells; muscle contraction; muscle pharmacology; muscle tension; muscle tone; muscular dystrophy; myofibrils; newborn animals; striated muscles

The long term objective of the proposed research project is to define the functional role of voltage gated Ca++ entry in skeletal muscle. Voltage and current clamp experiments will be carried out in isolated skeletal muscle from the frog with the cut fiber preparation in the vaseline gap technique. Myoplasmic Ca++ transients will be optically measured with Antipyrylazo III. Ionic currents, charge movement and changes in intracellular Ca++ concentration will be studied simultaneously. The slow Ca++ channel is located in the tubular system and it is too slow to be activated during a single action potential, however this is not the case for the recently described fast Ca++ channel. In initial experiments the effect of reducing external Ca++ on the Ca++ transient associated with the action potential will be investigated. In order to distinguish the activation of these channel in relation to charge movement and Ca++ transients, the pharmacology and modulation of fast and slow Ca++ channels will be studied in detail. In addition the recent described fast Ca++ channel will be further characterize in term of its localization, pharmacology and kinetic. These studies will be performed in a comparative way in preparations with variations of Ca++ channel currents such as the denervated muscle fiber, the end-plate region and the tail muscle from tadpoles. Ca++ channels were recently described in skeletal tonic fibers, where Ca++ entry may play a role in contraction. This point will be clarified by simultaneously measuring Ca++ currents, Ca++ transient and charge movement. An insight on the role of Ca++ channel activation will be obtained also from developmental studies, with measurements of Ca++ macroscopic and single currents that will be performed in primary cultures of skeletal muscle of new born rats. To define the physiological role of voltage gated Ca++ entry in skeletal muscle is a relevant problem in the medical sciences, since, Ca++ channel alterations have been recently described in muscle diseases such as muscular dysgenesis and muscle dystrophia.

拟议研究项目的长远目标是 确定电压门控Ca++进入骨骼肌的功能作用， 肌肉. 将进行电压钳和电流钳实验 从青蛙的骨骼肌中分离出来， 凡士林间隙技术制备。 肌浆Ca++ 瞬变将用安替比林偶氮III进行光学测量。 离子 电流、电荷运动和细胞内Ca++的变化 浓度将同时进行研究。 缓慢的Ca++ 通道位于管状系统中，并且它太慢而不能被 在单个动作电位期间激活，然而这不是 最近描述的快速Ca++通道的情况。 初始 实验研究了降低外源性Ca ~（++）对Ca ~（++） 将研究与动作电位相关的瞬态。 为了区分这些通道的激活与 电荷运动和Ca++瞬变，药理学和 快钙通道和慢钙通道的调节将在 详细 此外，最近描述的快速Ca++通道将是 进一步从定位、药理、 动力学 这些研究将以比较的方式进行， 具有变化的Ca++通道电流的制剂，例如 去神经肌纤维、终板区和尾肌 从蝌蚪。 钙离子通道最近被描述在骨骼肌中， 紧张性纤维，其中Ca++进入可能在收缩中起作用。 这一点将通过同时测量Ca++来阐明 电流、Ca++瞬变和电荷运动。 关于The Ca++通道激活的作用也将从 发育研究，测量Ca++宏观 和单一电流，将在原代培养物中进行， 新生大鼠骨骼肌。 来定义生理角色 骨骼肌中电压门控Ca++进入的相关性 在医学科学的问题，因为，Ca++通道改变 最近在肌肉疾病中被描述， 发育不全和肌肉营养不良。