par Desmedt, Jean Edouard 
;Hainaut, Karl
Référence Journal of physiology, 265, 2, page (565-585)
Publication Publié, 1977-02
;Hainaut, Karl Référence Journal of physiology, 265, 2, page (565-585)
Publication Publié, 1977-02
Article révisé par les pairs
| Résumé : | Ca movements in resting and in activated single giant muscle fibers of the barnacle were analyzed before and after exposure to dantrolene Na, a synthetic hydantoin derivative. In fibers microinjected with the photoprotein aequorin, the resting rate of light emission (resting glow) reversibly decreased upon exposure to dantrolene. Similar results were obtained if the fiber had first been equilibrated in a 0 Ca 1 mM EGTA medium. The influx of 45Ca into resting muscle fibers was not modified by 35 μM dantrolene which also failed to significantly reduce the influx of 45Ca into muscle fibers which had been depolarized by exposure to external solutions in which K+ had been increased to 60 or 200 mM. In fibers microinjected with 45Ca, the calcium efflux was reversibly decreased by dantrolene. This effect was still observed in 0 Ca medium and in 0 Ca 0 Na medium. A possible effect of dantrolene on the Na Ca exchange process at the outer membrane was excluded by showing that when the direction of the Ca2+ movement was inverted in aequorin loaded fibers by the sudden removal of Na+ from the external medium, a marked increase in the resting glow was recorded which was not affected by exposure to dantrolene. It is argued that the reduction of Ca2+ efflux by dantrolene does not result from any direct inhibitory effect on the metabolically driven Ca pump at the outer membrane, but that it is rather related to the reduction of the concentration of myoplasmic Ca2+ which is indeed demonstrated by the reduced resting glow. This in turn is thought to result from a shift in the balance between Ca2+ movements into and out of the intracellular storage sites, and namely the sarcoplasmic reticulum (SR). The Ca2+ transient in aequorin loaded fibers and the force of the isometric contraction elicited by imposed membrane depolarizations were markedly reduced by dantrolene. The electrochemical threshold for eliciting intracellular Ca2+ release was not significantly modified. The linear relation between membrane depolarization and Ca2+ transient became less steep. The process of sequestration of myoplasmic Ca2+ back into SR was not significantly affected by dantrolene which appeared to inhibit rather selectively the Ca2+ release from SR into the cytosol. |
