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4. Changes in external K concentration produced changes in the initially recorded resting potentials which follow the constant field theory using a ratio of Na:K permeabilities PNa/PK = 0-02. Changes in external C1 concentration produced little or no change in the resting potential or membrane resistance, indicating a low Cl permeability.5. In agreement with previous work, slow fibres showed a timedependent decrease in resistance ('delayed rectification') for membrane potentials more positive than -60 mV. 'Anomalous rectification' observed in twitch fibres was not seen in slow fibres. In high external K concentrations the resistance of slow fibres is almost unaffected by changes in membrane potential.6. Increasing the concentration of external Ca (up to isotonic) has two distinct effects on slow fibres. It increases Rm up to ten times, and it improves the stability of trans-membrane recordings, probably by reducing the leakage due to micropipette penetrations. Magnesium does not appear to have either of these effects.

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A BSTRACT Xylocaine and its derivatives act specifically at the neuromuscular junction within the concentration range 0.05 to 2.0 m. The charged form is the active form of the drugs. There is no correlation between "local anesthetic" activity and effect at the junction. Like d-tubocurarine, these drugs have little or no effect on quantum content, acetylcholinesterase activity, or the passive impedance of the muscle fiber. Yet they produce end plate potentials characterized by a brief, early component and a late, greatly prolonged component, as does procaine. Analysis of these changes in time course suggests that the drugs have little or no effect before receptors are activated by acetylcholine, but cause a decreased and often greatly prolonged response. Clear structure-activity relations indicate that the receptor to which the drugs bind to produce the prolonged response can be the receptor for acetylcholine. Comparison of the effects of the drugs on the end plate potential and on the response to iontophoretically applied acetylcholine also shows that the effects of Xylocaine depend on the time course of receptor activation and are quite different from the effects of dtubocurarine.The experiments reported here were prompted by previous studies on the effects of the local anesthetic procaine at the neuromuscular junction of frog skeletal muscle (4,10,20,21). Procaine has been found to depress the amplitude of the response of the postsynaptic receptors to acetylcholine (ACh) (4). But unlike d-tubocurarine (d-TC), which depresses the amplitude of the end plate potential (e.p.p.) without greatly altering its time course (rise time of 1-2 msec and half-time of fall 2-8 msec [9]) procaine produces e.p.p.'s that have an initial rapid transient (rise time 0.5-1 msec, half-time of fall 1 msec or less) followed by a greatly prolonged late falling phase (10). Maeno (20,21) has shown that this prolonged phase arises from a prolonged flow '44

1. The electrical and structural characteristics of ‘slow’ muscle fibres of the frog were studied in normal and denervated muscles, and in muscles undergoing re‐innervation by a mixed nerve containing large and small motor axons. 2. In agreement with previous studies, slow fibres in normally innervated muscles were incapable of producing action potentials. 3. Approximately 2 weeks after the sciatic nerve was transected or crushed, slow muscle fibres acquired the ability to generate action potentials. These fibres were positively identified as belonging to the slow type, because their passive‐electrical and ultrastructural characteristics remained essentially unchanged after the operations. 4. The action potential mechanism induced in slow fibres is sodium‐dependent, and is blocked by tetrodotoxin. 5. After long‐term re‐innervation by a mixed nerve, slow fibres lose their acquired ability to generate action potentials, presumably because small motor axons re‐establish connexion with the fibres. 6. It is concluded that the action potential mechanism of slow muscle fibres is under neural control, and is normally suppressed by small motor axons.

A kinetic scheme postulating the rapid formation of a partially active acetylcholine-receptor-drug complex from Xylocaine (or a derivative) and the active acetylcholine-receptor complex can account for the effects of Xylocaine and its derivatives at the neuromuscular junction. Transmembrane currents generated by an analogue computer programmed according to the scheme can exactly match end plate currents produced by nerve stimulation in the presence of the drugs. The scheme also accounts for the qualitatively different effects of the drugs on the end plate potential and on responses to iontophoretically applied acetylcholine. The analysis presented is consistent with very rapid reactions between acetylcholine and receptors, characterized by rate coefficients in the range 104 to 106 sec-'. It is based on the hypothesis that the activation of receptors by acetylcholine changes the structure of the receptors and thus their affinity for Xylocaine. The analysis does not require pharmacological separability of sodium and potassium conductances during the end plate current.Procaine, Xylocaine, and derivatives of Xylocaine depress and modify the response of the postsynaptic receptors of the neuromuscular junction to acetylcholine (ACh) (22,25). The most striking aspect of the effects of these drugs is the production of a prolonged component of the end plate potential (e.p.p.) that cannot be ascribed to an anticholinesterase action. In this respect, and in many other details, the actions of the drugs differ greatly from that of dtubocurarine (d-TC) and other chemicals that also depress the response of receptors. However, the site of action of Xylocaine and procaine, like that of d-TC, appears to be at the postsynaptic receptors (22,25). This suggests that these drugs modify the kinetics of the receptor response, although they do not produce a response themselves. Thus, an analysis of the effects of Xylocaine and procaine at the neuromuscular junction should offer the opportunity to find out more about the receptors themselves.

Fishes of widely differing evolutionary backgrounds possess organs specifically adapted to produce an external electric field. In most, the field produced by the electric organ is too weak to be of use as a weapon, hence the name "weakly electric fish," to distinguish them from the strongly electric freshwater electric eel (Electro phorus} and electric catfish (Malapterurus) or the marine Torpedo and Stargazers (Family Uranoscopidae) (Lissmann, 1951;Coates, 1947Coates, , 1954.Lissmann and others have shown by behavioral tests that -weakly electric fishes can detect changes in the conductivity of their surroundings (Lissmann, 1958;Lissmann and Machin, 1958 ;Machin and Lissmann, 1960 ;Wantanabe and Takeda, 1963). This is accomplished by using the electric organ as the energy source, and specialized cutaneous receptors as the receivers for a system of active electrolocation, although the actual mechanisms involved are different than first suggested (Machin and Lissmann, 1960;Bennett, 1967).