The mechanism of action of dantrolene sodium.
The mechanism of action of dantrolene sodium.
复制标题
丹曲林钠的作用机制。
DOI：
10.1097/00132586-197712000-00007
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发表时间：
1977
期刊：
影响因子：
--
通讯作者：
S. Bryant
中科院分区：
文献类型：
--
作者：
K. Morgan;S. Bryant
Dantrolene sodium is thought to affect some step in the excitation-contraction coupling process. Using a point voltage clamp to determine mechanical thresholds of individual fibers of frog, rat and goat skeletal muscle preparations, we found that dantrolene both raises (moves to more positive potentials) the rheobasic potential and increases the steepness of the strength-duration curve for mechanical threshold. The effect of raising the rheobase reaches a maximum at 1.2 x 10-5M dantrolene whereas the steepness effect occurs only at a saturating concentration (3.8x10-5M),indicating that dantrolene has two sites of action. The rheobase effect is absent below 18 degrees C (suggesting a phase transition) and it is competitively antagnoized by the calcium ionophore A23187 which can release calcium from the sarcoplasmic reticulum. The data indicate that dantrolene raises the rheobase by directly decreasing the release of calcium from the sarcoplasmic reticulum. We propose that dantrolene inhibits the movement of a natural calcium ionophore. Measurements of the voltage-dependent charge movement associated with excitation-contraction coupling showed that dantrolene did not significantly change the amount of charge moved. The time to peak of the ON current was not significantly changed, but that of the OFF current was significantly shortened. This action of dantrolene on the kinetics of the OFF current may account for its effect on the steepness of the strength-duration curve.
