Modification of excitation‐contraction coupling in locust skeletal muscle induced by caffeine

Abstract

Potassium contractures were recorded isometrically in locust extensor tibialis muscles. The graphs relating contracture tension to external potassium, and contractute tension to depolarization were of sigmoid shape. In normal circumstances, peak contracture tension was obtained with 100 mM/1 potassium saline at a depolarization level of about --lo mV. At a concentration of 2 mM/1, caffeine considerably lowered the mechanical threshold of the muscle fibres such that peak contracture tension was obtained with 40 mM/1 potassium saline, at a depolarization level of only -30 mV. Withdrawal of calcium ions from caffeine containing salines resulted in a loss of the contractile response to depolarization, and the lowering of the mechanical threshold was abolished. These results are consistent with the view that caffeine may activate muscle in vivo by accelerating calcium release from the sarcoplasmic reticulum and by suppressing active calcium binding by the reticular calcium pump. Since caffeine can activate depolarized muscle i t is suggested that caffeine short-circuits the normal excitation-contraction coupling channels to initiate a direct release of calcium ions from the sarcoplasmic reticulum without transient depolarization.For many years, caffeine has been known to possess the ability to potentiate the contraction of skeletal muscle (Goffart and Goutier, '50; Sandow and Brust, '66; Luttgau and Oetliker, '68; Huddart, '69a). In these investigations, the concensus view is that caffeine potentiates contraction by modifying the excitation-contraction coupling of muscle such that the mechanical threshold of the muscle fibres is considerably lowered. As a result of this action, potassium contractures in skeletal muscle may be modified by caffeine treatment such that maximal contracture tension is obtained at lower than normal potassium concentrations (Luttgau and Oetliker, '68; Huddart, '69b).In addition to the above action, caffeine causes persistent activation of the contractile component of the muscle fibres, and a further complicating factor is that caffeine is able to induce contractures in muscle in which the excitation-contraction coupling has been uncoupled by prolonged depolarization (Axelsson and Thesleff, '58; Caputo, '66; Huddart, '69a).Some of the above caffeine actions have already been briefly reported in insect skeletal muscle (Huddart, '69a), but in this latter study, the mechanism and site J. EXP. ZOOL., 171: 49-58.of caffeine activation were not conclusively elucidated. In this present study, the method of caffeine modification of excitation-contraction coupling in insect skeletal muscle has been examined in greater detail.Previous investigations have already decribed some of the characteristics of normal potassium contractures in various locust skeletal muscles (Hoyle, '61; Aidley, '65a,b). Since potassium contractures are ideal agents in indicating any alterations to mechanical thresholds and depolarization levels, they have been employed in this present study to characterize the event...

The effect of quinine on tension development, membrane potentials and excitation‐contraction coupling of crab skeletal muscle fibres

“…Although the triggering of the EC coupling events in some crustacean skeletal muscles does not appear to be dependent upon the attainment of a distinct mechanical threshold (Reuben, Brandt, Garcia & Grundfest, 1967), a distinct threshold exists in crab fibres (Huddart, 1969a), as is the case in vertebrate (Hodgkin & Horowicz, 1960) and many other arthropod skeletal muscles (Atwood, 1962;Edwards, Chichibu & Hagiwara, 1964;Hoyle, 1961;Hoyle & Smyth, 1963;Hagiwara, Takahashi & Junge, 1968;Huddart & Abram, 1969). Whereas caffeine significantly lowers the mechanical threshold of crab skeletal-muscle fibres (Huddart, 1969a), there is no evidence from this study that quinine has such an effect on crab muscle, although a lowering of mechanical threshold by quinine has 652 H. HUDDART QUININE AND CRAB SKELETAL MUSCLE been reported in frog skeletal muscle (Sandow et al 1964).…”

“…A further point of difference between the effect of caffeine and quinine on the initiation of EC coupling is that whereas caffeine has little effect on the membrane potential (Sandow et al 1964;Huddart, 1969 a;Chiarandini et al 1970), quinine reduces both resting and action potentials of crab skeletal muscle fibres. Initially quinine increases the duration of the action potential, but this is rapidly followed by reduction in amplitude and general depolarization of the muscle.…”

“…The best-known alkaloid potentiator of muscular contraction is caffeine, and much is now known about its mode of action on the trigger stages of the EC coupling at peripheral sites (Luttgau & Oetliker, 1968;Huddart, 1969a, b;Huddart & Abram, 1969) and on the terminal EC coupling stages within the muscle fibre (Sandow & Brust, 1966;Isaacson & Sandow, 1967a, b;Carvalho, 1968a;Isaacson, 1969;Huddart & Oates, 1970;Isaacson, Hinkes & Taylor, 1970).…”

“…Not only does it lower the mechanical threshold of the fibres (Etzensperger & Gasciolli, 1963; Sandow, Taylor, Isaacson & Seguin, 1964;Luttgau & Oetliker, 1968;Huddart, 1969a;Huddart & Abram, 1969) and thus prolong the active state, it also induces contractures in both normal and depolarized muscle (Axelsson & Thesleff, 1958;Caputo, 1966;Huddart, 1969a, b) and modifies the calcium control system of the sarcoplasmic reticulum (Isaacson & Sandow, 1967a, b;Carvalho, 1968a;Isaacson, 1969;Chiarandini, Reuben, Brandt & Grundfest, 1970), thus modifying the action of the relaxation factor.…”

“…One very interesting feature of the action of caffeine on skeletal muscle is its ability to initiate contractures in depolarized muscle (Axelsson & Thesleff, 1958;Caputo, 1966;Huddart & Abram, 1969). To locate the site of action of quinine on the EC coupling process, it was essential to check whether quinine also possessed the ability to activate uncoupled muscle.…”