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In previous studies on the role of calcium ions in excitation-contraction coupling in skeletal muscle (Frank, 1958(Frank, , 1960 it was demonstrated that removal of the extracellular calcium ions can abolish the potassium-induced contracture of the frog's toe muscle. It was also reported recently that the potassium-induced contracture can be restored if any one of several multivalent cations is added to the calcium-free solution bathing the muscle .In contrast to potassium, caffeine induces a contracture of skeletal muscle even in a completely depolarized muscle (Axelsson & Thesleff, 1958). Axelsson and Thesleff also showed that caffeine acts on the outer surface of the muscle cell. Unmodified caffeine-induced contractures occur in a calcium-free solution even after potassium-induced contractures have been completely abolished (Frank, 1960). This finding might indicate that caffeine induces contracture of a skeletal muscle by a process not involving calcium ions. However, Bianchi (1961) has shown that caffeine causes the release of calcium ions into a calcium-free solution bathing a muscle and has suggested that this displacement may be involved in caffeine-induced contractures.In the present study the potassium-induced contracture produced in calcium-free solutions containing various multivalent ions has been analysed further and compared with the caffeine-induced contracture. Evidence has been obtained supporting the concept that the production of contracture by caffeine is dependent upon the presence of a store of bound calcium ions in or on the muscle. The results also show that certain multivalent cations support potassium-induced contracture in a calciumfree solution by displacing calcium ions from the same site acted upon by caffeine.

Procaine and several general anaesthetics block production of action potentials in frog skeletal muscle fibres by a single mechanism of action, which suggests that there might be a common basic mechanism of action on neurones in the central nervous system. Procaine or cinchocaine given alone to intact white mice produced " excitement" and convulsions but when given 60 min after phenobarbitone they caused central nervous depression. Large, convulsant doses of procaine or cinchocaine abolished the righting reflex in mice previously treated with small, subanaesthetic doses of phenobarbitone. In contrast, leptazol only antagonized the depression produced by phenobarbitone. When applied directly to neuronally isolated slabs of cat cerebral cortex, procaine or pentobarbitone reduced the sizes of the surface negative and surface positive responses to direct electrical stimulation of the cortex. Leptazol had the opposite effect. When given systemically, procaine only increased the electrical threshold for the surface positive response recorded from the isolated slab; ether either increased or did not change this threshold, and leptazol either decreased or did not change it. These results are consistent with the suggestion that general and local anaesthetics have a fundamentally similar action on neurones in the central nervous system.

The mechanisms for the excitability changes produced by ether on the electrical activity of frog skeletal muscle were investigated by intracellular microelectrode techniques. Low concentrations of ether (less than 1%) increased excitability by increasing the 'effective resistance' between the inside and the outside of the fiber at the point of stimulation, thereby reducing the current needed to initiate an action potential. Higher concentrations decreased excitability by inhibiting the specific increase in sodium conductance which normally follows an adequate stimulus and is responsible for the rising phase of the action potential.

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