No abstract

Diverse potentiators of contraction have basically identical, activestate mechanical effects, but act by different membrane-mediated electromechanical coupling mechanisms. The falling phase of the action potential is greatly prolonged by Zn(2+) (0.1 mM) and UO(2)(2+) (0.5 to 1 microM), neither of which affects the mechanical threshold. Caffeine (1 mM), like the lyotropic anions, acts conversely. Thus changes in the duration and mechanical threshold of the action potential determine independent electromechanical coupling processes which can act individually, or conjointly in the action of other potentiators, in determining the duration of the active state and thus the potentiation of twitch tension.

1 mM caffeine, which produces only twitch potentiation and not contracture in frog sartorius muscle, increases both the uptake and release of ~Ca in this muscle by about 50 %, thus acting like higher, contracture-producing concentrations but less intensely. Quinine increases the rate of release of ~Ca from frog sartorius but not from the Achilles tendon. The thresholds for the quinine effect on 4~Ca release and contracture tension are about 0.1 and 0.5 mM, respectively, at pH 7.1. Quinine (2 mM) also doubles the uptake of ~Ca by normally polarized muscle. However, there are variable effects of quinine upon ~Ca uptake in potassium-depolarized muscle. Quinine (2 raM), increases the Ca, Na, and water content of muscle while decreasing the K content. Both caffeine (1 raM) and quinine (2 mM) act to release ~Ca from muscles that have been washed in Ringer's solution from which Ca was omitted and to which EDTA (5 inM) was added. These results, correlated with those of others, indicate that a basic effect of caffeine and quinine on muscle is to directly release activator Ca ~+ from the sarcoplasmic reticulum in proportion to the drug concentration. The drugs may also enhance the depolarization-induced Ca release caused by extra K + or an action potential. In respect to the myoplasmic Ca 2+ released by direct action of the drugs, a relatively high concentration is required to activate even only threshold contracture, but a much lower concentration, added to that released during excitation-contraction coupling, is associated with the condition causing considerable twitch potentiation.Caffeine and quinine affect frog skeletal muscle similarly in some respects. In low concentrations (caffeine, 1 mM; quinine, 0.1 raM) they increase the tension output of the twitch; i.e., they are twitch potentiators (for review, see , whereas in somewhat higher concentrations they not only potentiate the twitch but also engender contracture, though with considerable variability (caffeine: Axelsson

Research on the niechanical latelit period of contraction -the short interval of time between the instant of application of the stimulus and the onset of tension develowent -has given rise to one of the more controversial subjects in the field of muscle physiology. A major point of contention, in fact, has been the question of the very existence of mechanical latency. It is not necessary to review the general literature of the subject here for detailed summaries will be found in the work of Peo (1888), Rauh ( '22)' Fulton ( '26)' and Lindhard ( '31). Two points of special interest will be discussed, however. The first is the undue credence (e.g. Ritchie, '33) given to the relatively recent research of Roos ( '31, '32) whose experiments seemed to give incontrovertible support to the long-held view that no latent period will be registered if the inertia of the recording system is reduced to zero. The attention paid to ROOS' claim is hardly justified, for as Snyder ('36) states: "ROOS publishes very few of his observations, and bases his argument not on a statistical datum but apparently upon a few readings, that he considers crucial, and upon theoretical grounds. " The second point is the general lack of attention suffered by the investigation of Rauh ('22), which demonstrated for the first time the existence of a minute relaxation of frog skeletal muscle just prior to the beginning of tension rise.2 This finding is obviously of such great significance for the whole problem of mechanical latency that it Will be discussed in some detail.Rauh, having in mind the criticism that the latent period had no real existence in muscular response and that its presence in meclianograms Z A n earlier observation of a precontractilr relaxation seems to br present in the work of Ye0 (1888). It is not clear, however, whether this relaxation was similar to that observed by Rauh, or a stretching effect at the point of recording due t o the contraction of other parts of the muscle. A t any rate, Yeo states that "the elongation of the muscle commences after the ordinary latency is over," and this indicates that, whatever the nature of his actual records, the author did not think he was dealing with the type of relaxation later demonstrated by Rauh.