Effects of calcium "antagonists" on vertebrate skeletal muscle cells.
Effects of calcium "antagonists" on vertebrate skeletal muscle cells.
复制标题
钙“拮抗剂”对脊椎动物骨骼肌细胞的影响。
DOI：
10.1111/j.1749-6632.1988.tb33363.x
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发表时间：
1988
影响因子：
5.2
通讯作者：
Wanek,LA
中科院分区：
文献类型：
--
作者：
Helland,LA;Lopez,JR;Taylor,SR;Trube,G;Wanek,LA
临床上有效的骨骼肌松弛剂主要用于对中枢神经系统的影响。但它们也对肌肉收缩有直接影响，可能涉及Ca 2+通道。我们比较了丹曲林（一种已知对脊椎动物骨骼肌有直接作用的药物）与用作（1）松弛剂和（2）Ca依赖性兴奋-收缩偶联拮抗剂的其他物质的作用。孤立的完整的青蛙肌肉细胞注射的发光蛋白水母发光蛋白，膜电位的变化，细胞内Ca 2+瞬变，和收缩力进行了测量。丹曲林（10（-8）至10（-5）M）降低了Ca 2+瞬变的幅度，不影响其衰减速率，并降低了收缩力。我们还使用了一个集成的数字成像系统来记录显微镜下的变化，即肌原纤维的主动缩短和条纹间距的变化。与细胞中心附近的肌原纤维相比，丹曲林没有增加表面附近肌原纤维收缩之间的时间。因此，丹曲林不会通过干扰横向管状系统中的电流来抑制Ca 2+瞬变。以下各项实际上增加了动作电位诱发的Ca 2+瞬变和收缩力：巴氯芬（10（-7）至10（-5）M）低于氟地平（10（-6）M）低于甲丙氨酯（10（-7）至10（-3）M）低于利血平（10（-5）X 10（-4）M）低于普鲁卡因（10（-5）至比GABA（10（-5）M）低5 × 10（-4），比D-600（10（-6）M），比尼地林（10（-5）M）低5 × 10（-4）-完整骨骼肌肌浆网中的Ca ~（2+）通道被丹曲林明显抑制，但不被Ca ~（2+）拮抗剂抑制。
Clinically potent skeletal muscle relaxants are used primarily for their effects on the central nervous system. But they also have direct effects on muscle contraction that possibly involve Ca2+ channels. We compared the effects of dantrolene, an agent known to have a direct action on vertebrate skeletal muscle, with other substances used as (1) relaxants and (2) antagonists of Ca-dependent excitation-contraction coupling. Isolated intact frog muscle cells were injected with the photoprotein aequorin, and membrane potential changes, intracellular Ca2+ transients, and contractile force were measured. Dantrolene (10 (-8) to 10 (-5) M) decreased the amplitude of Ca2+ transients, did not affect their rates of decay, and reduced contractile force. We also used an integrated digital-imaging system to record microscopic changes, namely, active shortening in myofibrils and changes in striation spacing. Dantrolene did not increase the time between contraction in myofibrils near the surface compared with myofibrils near the center of a cell. Hence dantrolene does not suppress Ca2+ transients by disturbing current flow in the transverse tubular system. Each of the following actually increased Ca2+ transients and contractile force evoked by action potentials: baclofen (10 (-7) to 10 (-5) M) less than flordipine (10 (-6) M) less than meprobamate (10 (-7) to 10 (-3) M) less than chlordiazepoxide (10 (-5) X 10 (-4) M) less than procaine (10 (-5) to 5 X 10 (-4] less than GABA (10 (-5) M) less than D-600 (10 (-6) M) less than nylidrin (10 (-5) M)--in order of increasing potency. Ca2+ channels in the sarcoplasmic reticulum of intact skeletal muscle are evidently inhibited by dantrolene but not by Ca2+ antagonists.