SUMMARY1. Contractile responses in short twitch-type snake muscle fibres have been studied. These fibres are sufficiently short to allow fairly uniform changes in membrane potential along their length when current is passed through an intracellular micropipette. Active sodium permeability changes were blocked with tetrodotoxin (TTX), procaine, or by using solutions low in sodium. Current and voltage micropipettes were used to voltage-clamp these fibres. Depolarization steps to about -40 mV evoked contractile responses, maximal tension being developed between -10 and 0 mV. The relation between contraction and membrane potential was sigmoid.2. Depolarization beyond a critical threshold produced an increment of outward current which inactivated with time. The threshold for this delayed rectification was normally similar to the threshold for contractile activation. Fibres exposed to high potassium showed a reversal of this inactivating current to slightly super-threshold depolarizing pulses. At membrane potentials near 0 mV, no inactivating current was noted, while stronger depolarizing pulses produced an inactivating current in the normal direction. Fibres in high potassium show the same threshold for initiation of contraction as in normal solution.3. Thiocyanate, nitrate, and caffeine shifted the relation between membrane potential and contraction toward higher levels of membrane potential. The threshold for inactivating rectifying current failed to shift to a corresponding extent, although some shift in rectification which did not inactivate was evident.4. When depolarization was maintained, contractile tension was maximal for several seconds, then gradually disappeared. The rate of this contractile inactivation depended upon the level of depolarization.

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The cardiotoxic effects of emetine dihydrochloride on mechanical and electrical activity were studied in isolated preparations (papillary muscles, sinoatrial and atrioventricular nodes, ventricular myocytes) of the guinea‐pig heart. Force of contraction was measured isometrically, action potentials and maximum rate of rise of the action potential were recorded by means of the intracellular microelectrode technique. Single channel L‐type calcium current (Ba2+ ions as charge carrier) was studied with the patch‐clamp technique in the cell‐attached mode. Emetine dihydrochloride (8–256 μm) reduced force of contraction in papillary muscles and spontaneous activity of sinoatrial and atrioventricular nodes concentration‐dependently; the negative inotropic effect was abolished when the extracellular Ca2+ concentration was increased. Maximum diastolic potential, action potential amplitude, maximum rate of rise of the action potential and the slope of the slow diastolic depolarization were decreased by emetine in sinoatrial as well as atrioventricular nodes, while action potential duration was prolonged in both preparations (1–64 μm). The amplitude of the L‐type calcium single channel current was not altered by emetine dihydrochloride, while average open state probability was decreased concentration‐dependently (10, 30 and 60 μm). The most prominent effect of emetine dihydrochloride on single channel current was an increase of sweeps without activity. At 60 μm, emetine dihydrochloride caused a decrease of the mean open time and an increase of the mean closed time. The number of openings per record and number of bursts per record were reduced. It is concluded that emetine dihydrochloride produces an L‐type calcium channel block which might contribute to its cardiac side effects.

SUMMARY1. Contractile repriming has been studied in voltage-clamped snake twitch muscle fibres. Maintained depolarization causes a contractile response which inactivates after a few seconds. Repolarization of the fibre can restore its ability to contract to a subsequent depolarization. This restoration, or repriming, depends on the magnitude and the duration of the repolarization. At -100 mV the minimal period of repolarization which restores contractile response is 0-38 sec. The time for recovery to half maximal tension is about 0-68 sec, and restoration is complete at about 4 sec.2. Repolarization to smaller levels of membrane potential results in a slower rate of repriming. For example, at -60 mV the mean minimal time for repriming was 2-89 sec, and nearly 17 sec of repolarization was required for full restoration of contractile response.3. The rate of reprising was not influenced by lowering the external sodium concentration.4. Repriming could be produced by repetitive, brief pulses of repolarization.5. The restoration of contractile response and of outward inactivating current showed similar time courses.

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