SODIUM CHANNEL GATING IN MODELS OF MYOTONIA

肌强直模型中的钠通道门控

• 批准号: 3412643
• 负责人: ROBERT LOUIS RUFF
• 金额: $ 1.18万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3412643
• 关键词: SDS polyacrylamide gel electrophoresis; cyclic compound; disease /disorder model; gel electrophoresis; histochemistry /cytochemistry; laboratory rat; membrane potentials; muscle cells; myofibrils; myotonia congenita; sodium channel; striated muscles; voltage /patch clamp

The objectives of this proposal are: 1) to study sodium channel inactivation in rat skeletal muscle, and 2) to investigate rat model of human muscle myotonic disorders in which membrane excitability may be impaired. Two hypotheses about sodium channel gating will be tested. First, that sodium currents are increased by treatments which produce myotonia in rat skeletal muscle. Second, that the increase in sodium current density is due to an alteration in voltage-dependent sodium channel inactivation. The techniques employed are: 1) the loose-patch voltage clamp will be used to measure sodium currents, and 2) the fiber type of single fibers will be determined by histochemical staining and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The experiments measure sodium currents in control and myotonic muscle using techniques developed in this laboratory that permit stable current recordings of cells for several hours. Myotonia in rat muscle will be produced by: 1) bathing a fiber in a chloride- deficient solution, 2) treating fibers with aromatic carboxylic acids to reduce chloride conductance, and 3) treating rats with 20, 25-diazacholesterol. The voltage dependence of sodium channel fast and slow inactivation will be studied to examine whether changes in sodium current density can be attributed to alterations in fast or slow inactivation. These projects will provide 1) new information on the excitability of mammalian skeletal muscle; and 2) possibly new information on the pathophysiology of different forms of myotonia.

本课题的目的是：1)研究钠离子通道

项目成果

Calcium-tension relationships of muscle fibers from patients with periodic paralysis.

周期性麻痹患者肌纤维的钙-张力关系。

• DOI: 10.1002/mus.880140907
• 发表时间: 1991
• 期刊: Muscle & nerve
• 影响因子: 3.4
• 作者: Ruff,RL

How myasthenia gravis alters the safety factor for neuromuscular transmission.

• DOI: 10.1016/j.jneuroim.2008.04.038
• 发表时间: 2008-09-15
• 期刊: Journal of neuroimmunology
• 影响因子: 3.3
• 作者: Ruff RL;Lennon VA
• 通讯作者: Lennon VA

Insights into possible skeletal muscle nicotinic acetylcholine receptor (AChR) changes in some congenital myasthenias from physiological studies, point mutations, and subunit substitutions of the AChR.

通过生理学研究、点突变和 AChR 亚基替换，深入了解某些先天性肌无力中骨骼肌烟碱乙酰胆碱受体 (AChR) 可能发生的变化。

• DOI: 10.1111/j.1749-6632.1993.tb22928.x
• 发表时间: 1993
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Kaminski,HJ;Ruff,RL
• 通讯作者: Ruff,RL

Na+ channel distribution and inactivation properties of human type 1 and 2 muscle fibers.

人 1 型和 2 型肌纤维的 Na 通道分布和失活特性。

• DOI: 10.1111/j.1749-6632.1993.tb22923.x
• 发表时间: 1993
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Ruff,RL;Whittlesey,D
• 通讯作者: Whittlesey,D

Na current density at and away from end plates on rat fast- and slow-twitch skeletal muscle fibers.

大鼠快肌纤维和慢肌纤维终板处和远离终板的 Na 电流密度。

• DOI: 10.1152/ajpcell.1992.262.1.c229
• 发表时间: 1992
• 期刊: The American journal of physiology
• 作者: Ruff,RL