The characteristics and the mechanism of the biphasic potas

Summary Manganese ions are known to inhibit the calcium spike in crayfish and barnacle. In frog sartorius muscle, we found that Mn++ inhibits the peak tension of twitch, tetanus, and potassium contracture and also the rate of rise and relaxation of tension. The inhibiting effect of Mn++ increased with increasing concentration (1-10 mM). The magnitude of resting potential and the amplitude of action potential were not significantly affected, but the negative afterpotential was enhanced by 10 mM Mn++. At this concentration the peak tension of twitch, tetanus, and potassium contracture was almost completely inhibited. In 10 mM Mn++, the steep initial rise of tension in caffeine contracture was abolished, but the subsequent slow rise in tension was not affected. The peak tension was reduced by about 30 %. Mn++ actually activated the Mg++-activated ATPase of myofibrils from rabbit skeletal muscle and decreased the extra Ca-induced splitting of ATP by the sarcoplasmic reticulum. These results indicate that manganese ions inhibit excitation-contraction coupling by acting on the transverse tubular system and possibly terminal cisternae of the sarcoplasmic reticulum.Recently, specific action of manganese ions on certain muscles has been noticed. FATT andGINSBORG (1958), andHAGIWARA andNAKAJIMA (1966) reported that manganese ions inhibit the calcium spike in the muscles of crayfish and barnacle. On the other hand, FRANK (1960) reported that manganese ions can be substituted for external calcium ions in frog skeletal muscle, and JENDEN and REGER (1963) showed that manganese ions in low concentration prevent the deterioration of membrane potential of frog skeletal muscle in calcium-free solution. In these reports, however, the effect of manganese ions on the excitation-contraction coupling in this muscle were not studied in detail.Contraction and relaxation in skeletal muscle are generally considered to be caused by calcium release and uptake by the sarcoplasmic reticulum. However,

The effect of dantrolene sodium on"inactivation 1 and 2"

The time course of the inhibition of peak tension (inactivation) of potassium contracture induced by conditioning depolarization with 10, 15, 20 and 30 mm K+ was examined, using single twitch fibers from the frog semitendinosus muscle. The time-dependence curve of the inactivation was biphasic, consisting of the first phase and the second

The effect of dantrolene sodium, 1-[5-(p-nitrophenyl)furfurylideneamino] hydantoin sodium hydrate, on electrical and mechanical response in frog skeletal muscles (whole muscles or single fibers) and on the biochemical properties of contractile proteins and fragmented sarcoplasmic reticulum isolated from frog or rabbit skeletal muscle was investigated. The peak tensions of twitch, tetanus and potassium contracture were significantly inhibited by dantrolene, without affecting the magnitude of resting potential, the amplitude and duration of action potential and the negative afterpotential. On the other hand, ATPinduced shortening of glycerol-extracted rabbit psoas muscle fibers, ATPase activity of frog myofibrils and Ca release induced by caffeine, Ca uptake and ATPase activity of fragmented sarcoplasmic reticulum of frog or rabbit muscle were not affected by dantrolene. Caffeine contracture was partially inhibited by dantrolene and was almost unchanged by it in potassium-depolarized muscle fiber. Nitrate ions and low concentration of caffeine rapidly recovered the twitch inhibition induced by dantrolene. These results suggested that dantrolene acts on the membrane of transverse tubules and possibly the triadic junction and that it inhibits the inward movement of Ca and subsequently decreases the release of activator Ca from sarcoplasmic reticulum.