Effects of toxin II from the sea anemone Anemonia sulcata on contractile and electrical responses of frog skeletal muscle fibres

The effects of Anemonia sulcata toxin II (ATX-II) were studied on mechanical and electrical activities of frog muscle fibres isolated from semitendinosus or tibialis anterior muscles of Rana temporaria (2.8-7.7 degrees C). In concentrations ranging between 7.7 and 100 microM, ATX-II greatly potentiated the isometric twitch of single muscle fibres in a time-dependent manner. Increase in twitch amplitude by ATX-II was associated with an increase in time to peak tension and time from peak tension to half relaxation. ATX-II caused no change in maximum force production during fused tetanus, but the tension was maintained for several seconds after the cessation of stimulation. Such long tetanic contractions were also obtained in low-Na Ringer solution, but their duration was somewhat shorter. No specific action of ATX-II was detected on relaxation kinetics during a tetanus. The twitch potentiating effect of ATX-II was markedly increased by 3,4-diaminopyridine. Action potentials recorded from single muscle fibres in the presence of ATX-II showed a delayed onset of repolarization with a reduced rate of fall. In addition, ATX-II caused repetitive spontaneous firing of action potentials after the cessation of tetanic stimulation. ATX-II (3.3 - 10 microM) also increased action potential duration by reducing the rate of repolarization in surface fibres of formamide-treated sartorius or cutaneous pectoris muscles (20 degrees C) stimulated indirectly or directly. The potentiation of twitch force and the prolongation of contractions caused by tetanic stimulation can be attributed to the membrane action of ATX-II, which leads to prolongation of action potentials, to repetitive muscle firing and to the appearance of plateau potentials.     

DIRECT ACTION OF 4-AMINOPYRIDINE ON THE CONTRACTILITY OF A FAST-CONTRACTING MUSCLE IN THE CAT

The effects of 4-aminopyridine on the contractility of the fast-contracting tibialis anterior and the slow-contracting soleus muscles of cats under chloralose anaesthesia have been studied. 2. 4-Aminopyridine, in doses of 0.5 mg/kg and above, produced a slowly developing increase in the twitch tension of directly stimulated chronically denervated and of indirectly stimulated innervated tibialis anterior muscles, but had little or no effect on twitches of soleus muscles. The effect on innervated tibialis anterior muscles was more pronounced than that on chronically denervated muscles, but it was nevertheless concluded that the whole effect on innervated muscles was the result of a direct action on the muscle fibres. The simultaneously occurring facilitatory action on neuromuscular transmission, which is manifested in the anti-curare action of 4-aminopyridine, had a faster time-course and occurred in both the tibialis anterior and the soleus muscles. 3. 4-Aminopyridine antagonized dantrolene sodium on the tibialis anterior muscle but not on the soleus muscle. The antagonism could be described as physiological antagonism since it simply reflected the opposing actions on contractility of the two drugs. 4. 4-Aminopyridine was without effect on maximal tetanic tension of either the tibialis anterior or the soleus muscle. 5. It seems clear from the literature that a species difference exists with regard to the ability of 4-aminopyridine to increase muscle contractility. The results described in this paper show that muscle differences within the same species also exist.     

Blocking effects of hypaconitine and aconitine on nerve action potentials in phrenic nerve-diaphragm muscles of mice

The mechanisms of neuromuscular blockade by hypaconitine and aconitine were investigated electrophysiologically in isolated phrenic nerve-diaphragm muscles of mice. Hypaconitine (0.08-2 microM) and aconitine (0.3-2 microM) depressed the nerve-evoked twitch tension, without affecting the contraction evoked by stimulation of the muscle. At the concentrations of hypaconitine (up to 5 microM) and aconitine (up to 2 microM) that depressed the nerve-evoked twitch tension, the resting membrane potential of the muscle cells was unchanged. Hypaconitine (0.1-2 microM) and aconitine (2 microM) blocked the end-plate potential (epp), without affecting the amplitude of the miniature epp (mepp). The quantal content of end-plate potentials was decreased by these agents in parallel with the decrement in amplitude. The nerve compound action potential was inhibited by hypaconitine (5 microM) and aconitine (2-10 microM), as well as by 1 microM tetrodotoxin (TTX). When the nerve compound action potential was completely blocked by 2 microM aconitine, the muscle action potential was unaffected, although 1 microM TTX suppressed both potentials to the same degree. These results indicate the neuromuscular blockade produced by hypaconitine and aconitine were caused by reducing the evoked quantal release. The mechanism of this effect was attributed mainly to blocking of the nerve compound action potential.     

Neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin, astromicin, isepamicin and netilmicin on the diaphragm and limb muscles in the rabbit

Aminoglycoside antibiotics are known to produce a depression of neuromuscular function which may cause prolonged paralysis of respiratory muscles. However, differences in the effects of aminoglycoside antibiotics on diaphragm and limb muscles have not been investigated. We determined the neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin sulfate, astromicin sulfate, isepamicin sulfate and netilmicin sulfate on the diaphragm, tibialis anterior and soleus muscles in anesthetized rabbit nerve-muscle preparations. Neuromuscular block was assessed by mechanical response with single twitch stimulation. Cumulative drug dose-response curves were obtained for three different muscles in 24 rabbits. The mean ED(50) and ED(95) of the antibiotics in diaphragm, tibialis anterior and soleus muscles were calculated. The neuromuscular blocking effects of all the aminoglycosides on ED(50) and ED(95) values were in the order of soleus > tibialis anterior > diaphragm, and soleus > diaphragm > tibialis anterior, respectively. The ED(50) ratios for the tibialis anterior and soleus muscles were approximately 1.5 and 2.7 times greater than that for the diaphragm.     

The effect of 3,3-dipyridylmethyl-1-phenyl-2-indolinone on the neuromuscular transmission in the rodent skeletal muscles.

The effects of a cognition enhancer, 3,3-dipyridylmethyl-1-phenyl-2-indolinone (DPMPI) (21.5-645 microM), on neuromuscular transmission were studied electrophysiologically on diaphragms of mouse and rat and the soleus muscle of rat. The drug DPMPI (21.5-645 microM) increased both direct and indirect twitch tension of mouse diaphragm. It also increased (a) the frequency of miniature endplate potentials and (b) the quantal content of endplate potential. However, DPMPI (64.5 microM) affected neither the amplitude of the directly elicited action potential of soleus muscle in the rat nor the magnitude of the resting membrane potential of mouse diaphragm, although DPMPI (215 microM) decreased the amplitude of the compound action potential of phrenic nerve. Based on these results, it is concluded that DPMPI had several effects on neuromuscular transmission, i.e. it (a) facilitated the transmitter releasing process of the motor nerve terminal, (b) decreased the conduction in the phrenic nerve and (c) increased the directly elicited twitch tension.     

Effects of isoprenaline on contractions of directly stimulated fast and slow skeletal muscles of the guinea-pig

1. The actions of isoprenaline on the contraction and the resting potential of the isolated extensor digitorum longus (EDL), a fast contracting muscle, and the soleus, a slow contracting muscle, of the guinea-pig were investigated. Twitch tension was elicited by direct supramaximal stimulation and recorded isometrically.2. The twitch tension of EDL elicited by pulses of 0.5-10 ms duration was increased in the presence of isoprenaline (1 mug/ml). Isoprenaline increased the twitch tension of the soleus elicited by a pulse of more than 5 ms duration, but decreased it when elicited by a pulse of less than 1 millisecond. These effects were blocked by propranolol (1-3 mug/ml) but not by phentolamine (1-5 mug/ml).3. In EDL, isoprenaline prolonged the time to peak tension and the half-relaxation time. The twitch of the soleus was shortened by isoprenaline due to an acceleration of relaxation. These findings were independent of stimulus duration.4. The potentiating effects of isoprenaline on the twitch tension of EDL and the soleus were not observed in K(+)-free Krebs solution and were abolished by ouabain (1 mug/ml) and by reduction of the temperature from 33 degrees to 18 degrees C. The effects of isoprenaline on the relaxation proces were not affected by these treatments.5. In EDL, the resting potential increased from 77.3 mV to 78.5 mV after isoprenaline, whereas in the soleus it increased from 69.1 to 74.7 mV. These effects were blocked by propranolol, K(+)-deficiency, ouabain, and cooling to 18 degrees C. Hyperpolarization by isoprenaline was increased by substitution of isethionate for the external chloride.6. There was a good correlation between the potentiation of the mechanical response and the hyperpolarization of the membrane by isoprenaline. The hyperpolarization seems to be due to activation of the Na(+)-K(+) pump.     

ACTIONS OF DANTROLENE SODIUM ON CONTRACTIONS OF THE TIBIALIS ANTERIOR AND SOLEUS MUSCLES OF CATS UNDER CHLORALOSE ANAESTHESIA

SUMMARY 1. Dantrolene depresses the tension of directly or indirectly elicited twitches and tetaní of the tíbíalís anteríor and soleus muscles of cats under chloralose anaesthesia, without affecting the gross muscle action potentials.
2. The decrease in twitch tension is associated with slowed rates of rise of tension and of relaxation, but there is no change in the time to peak tension. The decrease in maximal tetanic tension is associated with a slowed rate of rise of tension, but there is no change in the rate of relaxation. It is concluded that dantrolene decreases the intensity of the active state, possibly by impairing the release of Ca²⁺ from the sarcoplasmic reticulum.
3. The soleus muscle is slightly more resistant than the tibialis anterior muscle to the action of dantrolene, and maximal tetani of both muscles are much more resistant than twitches.
4. Adrenaline, theophylline and quazodine produce effects on the dantrolene-depressed twitches that are proportionately the same as those produced on the control twitches; there is no evidence of a specific antagonistic effect of any of these drugs.
5. Tetanic stimulation of the tibialis anterior muscle but not the soleus muscle causes a temporary relief of the twitch depression produced by dantrolene.     

Post-tetanic and drug-induced repetitive firing in the soleus muscle of the cat

1. The effects of a high frequency indirect tetanus on the responses to subsequent infrequently applied nerve shocks have been compared in the tibialis anterior and soleus muscles of cats and rabbits.2. Post-tetanic augmentation of twitches in the cat soleus muscle was shown to be partly due to repetitive firing and partly due to increased synchronization of the muscle fibre response. Post-tetanic repetitive firing was not evident in the responses of the other three muscles studied.3. Post-tetanic repetitive responses in the cat soleus muscle and nerve did not originate in the nerve trunk and were not produced by direct muscle stimulation; they were abolished by doses of tubocurarine smaller than those necessary to reduce the twitch tension below the pre-tetanic level. These findings support the conclusion of others that the repetitive firing originates at the neuromuscular junction.4. The repetitive firing could not be explained by an increase in the sensitivity of the motor endplates to acetylcholine, suggesting that an increase in and/or a prolongation of the output of transmitter from the motor nerve contributes to it.5. The cat soleus muscle was shown to be more sensitive to neostigmine than were the other three muscles studied, and acetylcholinesterase determinations showed that this muscle possesses less enzyme activity.6. It is concluded that an increase in transmitter output, coupled with a weaker cholinesterase activity, probably accounts for the post-tetanic repetitive activity in the cat soleus muscle.7. Post-tetanic repetitive firing was absent in cat soleus muscles which had been cross-innervated with the nerve formerly innervating a fast-contracting muscle.     

Repetitive muscle responses induced by crotamine.

The sustained contractions of the dog tibialis anterior muscle and the rat gastrocnemius which may appear after a tetanus or twitch or spontaneously in crotamine injected animals are associated with the discharge of high frequency and small amplitude potentials. They are, therefore, asynchronous tetanic contractions. These potentials are similar to those observed in myotonia. The potentiated maximal twitch observed in crotamine injected dogs is actually a brief tetanus.     

TETANIC FADE DURING PARTIAL TRANSMISSION FAILURE PRODUCED BY NON-DEPOLARIZING NEUROMUSCULAR BLOCKING DRUGS IN THE CAT

1. A comparison has been made of the effects of three acetylcholine antagonists—hexamethonium, tubocurarine and pancuronium—on maximal tetani of limb muscles of cats under chloralose anaesthesia. In most experiments, the indirectly stimulated soleus muscle was studied, but observations were also made on the tibialis anterior and flexor digitorum longus muscles. 2. When neuromuscular block was produced by intra-arterial injections of the acetylcholine antagonists, tetanic tension, though depressed in amplitude, did not wane and there was little or no post-tetanic relief of the block as judged by the amplitude of subsequent twitches. On the other hand, during similar degrees of block produced by intravenous injections, tetanic tension rapidly waned, and, after the tetanus, transmission was temporarily facilitated, as evidenced by an increase in the amplitude of post-tetanic twitches. 3. Intravenously injected hexamethonium caused complete waning of tetanic tension in doses too small to depress twitch amplitude and which caused only a small depression of peak tetanic tension. In contrast, pancuronium caused only partial tetanic fade even in doses that produced pronounced depressions of twitch and tetanic tensions. The effects of tubocurarine fell between these extremes. 4. The results suggest that depression of peak tension and tetanic fade are independent effects of acetylcholine antagonists. It is postulated that the former is a consequence of block of post-junctional cholinoceptors, whereas the latter arises from an action at pre-junctional cholinoceptors. 5. The results obtained, together with those of other workers, led to the suggestion that transmitter acetylcholine, in addition to evoking the endplate potential, acts on the nonmyelinated nerve terminals in a positive feed-back mechanism that mobilizes transmitter to keep pace with release during high frequencies of stimulation.     

Induction of giant miniature end-plate potentials during blockade of neuromuscular transmission by textilotoxin

The present study investigated the action of textilotoxin, isolated from the venom of the Australian common brown snake Pseudonaja textilis, on neuromuscular transmission in isolated toad nerve-muscle preparations. Initial muscle twitch tension experiments revealed a triphasic pattern of changes in muscle tension and a irreversible binding action of textilotoxin (10 g/ml) similar to other snake -neurotoxins. This was characterised by an initial depression of twitch tension, followed by a period of enhanced tension, eventually leading to a reduction in tension to complete neuromuscular blockade.These actions on muscle tension were investigated further by assessing the action of textilotoxin on end-plate potential amplitude (EPP). This revealed a similar triphasic alteration of the nerve-evoked release of acetylcholine from the motor nerve terminal. These actions on acetylcholine release were confirmed to be of a presynaptic origin since the modal amplitude of miniature end-plate potentials (MEPPs) was not reduced and in twitch tension experiments the muscle still contracted in response to direct muscle stimulation when nerve-evoked release was completely blocked.Interestingly dramatic effects were observed on the spontaneous release of acetylcholine, including an marked increase in MEPP frequency, a skewing of the MEPP amplitude frequency histogram to the right, and a resultant increase in the number of giant MEPPs. These results indicate that textilotoxin causes a presynaptic blockade of neuromuscular transmission involving a disruption of the regulatory mechanism that controls acetylcholine release.     

The effects of beta-adrenoceptor activation on contraction in isolated fast- and slow-twitch skeletal muscle fibres of the rat.

1. The aim of the experiments was to examined the effects of beta-adrenoceptor activation on twitch and tetanic contractions in fast- and slow-twitch mammalian skeletal muscle fibres. Isometric force was recorded from bundles of intact fibres isolated from the normal and denervated slow-twitch soleus and normal fast-twitch sternomastoid muscles of the rat. 2. Terbutaline (10 microM), a beta 2-adrenoceptor agonist, induced an average 15% potentiation of peak twitch and peak tetanic force in normal soleus fibres and abbreviated twitch and tetanic relaxation. In white- and red-sternomastoid fibres, 10 microM terbutaline potentiated peak twitch force by about 7% and slowed twitch relaxation. 3. The potentiation of twitches and tetani by terbutaline was quantitatively similar in normal and denervated soleus fibres. However, in contrast to the normal soleus, terbutaline slowed twitch relaxation and had no effect on tetanic relaxation in denervated soleus fibres. 4. Adrenaline (10 microM) increased peak tetanic force by about 7% in both normal and denervated soleus fibres. 5. Exposure to (+/-)-propranolol (0.1 microM), a general beta-adrenoceptor blocker, completely abolished the tetanus potentiation by terbutaline. 6. Dibutyryl-cyclic AMP (2 mM) mimicked the effects of 10 microM terbutaline on peak tetanic force and tetanic relaxation in normal and denervated soleus fibres. Dibutyryl-cyclic AMP also potentiated peak twitch force in denervated soleus fibres but only after a brief period of twitch depression: the twitch depression might be due to butyrate.(ABSTRACT TRUNCATED AT 250 WORDS)     

EFFECTS OF CATECHOLAMINES, CYCLIC NUCLEOTIDES AND PHOSPHODI-ESTERASE INHIBITORS ON CONTRACTIONS OF SKELETAL MUSCLES IN ANAESTHETIZED CATS

SUMMARY 1. The actions and interactions of compounds with phosphodiesterase-in-hibiting activity and of sympathomimetic amines have been studied on contractions of skeletal muscles in chloralose-anaesthetized cats treated with bethanidine and in which the adrenals were excluded from the circulation.
2. Compounds with phosphodiesterase-inhibiting activity, ICI 63,197, ICI 58,301, papaverine, theophylline, and dipyridamole, potentiated isoprenaline in its depressant effect on tension and fusion of incomplete tetanic contractions of the slow-contracting soleus muscle, the order of potency being as listed. ICI 63,197 and theophylline also potentiated adrenaline and salbutamol in depressing contractions.
3. ICI 63,197 potentiated isoprenaline in its enhancing effect on tension and degree of fusion of incomplete tetanic contractions of the fast-contracting tibialis anterior and flexor digitorum longus muscles.
4. The results are compatible with the hypothesis that the effects of sympathomimetic amines on muscle contractility are mediated by cyclic adenosine-3',5'-monophosphate, although this nucleotide and its dibutyryl analogue, injected intra-arterially, were themselves without any consistent effect.
5. High doses of ICI 63,197, ICI 58,301, papaverine and dipyridamole, themselves produced isoprenaline-like effects on the soleus muscle. These effects were partially antagonized by (±)-propranolol, (+)-propranolol, or sotalol. The (+)-isomer of propranolol was only about ten times less potent than racemic propranolol in this respect. This antagonistic action of propranolol and sotalol appeared to be independent of β-adrenoceptor blockade.     

Effects of 3,4-diaminopyridine on mechanical and electrical responses of frog single muscle fibres

The effects of 3,4-diaminopyridine (3,4-DAP) were studied on isolated muscle fibres of the frog in concentrations ranging between 0.025 and 5.0 mM. Isometric twitch and tetanus responses were recorded at temperatures between 2.5 and 3.9 degrees. 3,4-DAP caused a concentration-dependent increase in twitch amplitude, maximum effects being obtained at a concentration of 3 mM with a mean increase in tension of 70 +/- 12% of control (n = 7). 3,4-DAP in 3 mM concentration had only a slight increase in initial rate of rise of twitch tension (mean increase 8 +/- 4%) but increased the time to half peak tension by 59 +/- 9% and the time from peak tension to half relaxation by 78 +/- 10%. No significant effect of 3,4-DAP was observed on the initial rate of rise and total amplitude of the isometric tetanus. The twitch potentiating effect of 3,4-DAP developed gradually with the number of times the fibre was stimulated and reached a maximum level after 40-50 stimulations. A gradual increase in the duration of the action potential was also observed. It is suggested that 3,4-DAP, like 4-aminopyridine, potentiates the twitch by means of prolonging the duration of the action potential.     

Electrophysiological effects of propafenone on isolated guinea-pig ventricular muscle and sheep Purkinje fibres

The electrophysiological effects of propafenone on transmembrane potentials were studied in sheep Purkinje fibres and guinea-pig ventricular muscle. In both preparations propafenone decreased the amplitude and Vmax of the action potential and shifted the resting membrane potential to less negative values. In Purkinje fibres, propafenone also slowed the conduction velocity and shortened the action potential duration whereas in ventricular muscle it had no effect on action potential duration. Propafenone also suppressed: the normal automatic mechanism in Purkinje fibres as well as the automaticity induced by BaCl2 and isoprenaline in ventricular muscle fibres with high resting membrane potential (between -75 mV and -85 mV), the abnormal automatic mechanisms, including the slow action potentials induced by BaCl2 and isoprenaline in ventricular muscle and Purkinje fibres depolarized above -55 mV, respectively, and the delayed after-depolarizations induced by ouabain in Purkinje fibres and ventricular muscle. The possible mechanisms responsible for the cardiac effects of propafenone and the therapeutic implications of these electrophysiological effects are discussed.     

Effects of increasing the frequency of twitches and of isoprenaline on maximal twitches and cyclic AMP levels in slow- and fast-contracting cat skeletal muscles

Increasing the frequency of twitches and treatment with isoprenaline have been compared for effects on twitch tension, tension-time integral and cyclic adenosine 3', 5'-monophosphate (cyclic AMP) levels in the slow-contracting soleus muscle of cats, anaesthetized with chloralose and pentobarbitone. The effect of change in frequency of contractions on cyclic AMP in the fast-contracting extensor digitorum longus muscle was also examined. Although both isoprenaline and increasing the frequency of contractions depressed twitch tension in the soleus, only isoprenaline enhanced cyclic AMP levels. The effects of isoprenaline were independent of the existing frequency of contractions of the muscle. Increasing the frequency of contractions enhanced twitches in the extensor digitorum longus muscle but did not change cyclic AMP levels. It is concluded that cyclic AMP may mediate effects of beta-adrenoceptor agonists but not those caused by increasing the frequency of contractions on slow- or fast-contracting skeletal muscles.     

Effects of the sea anemone Anemonia sulcata toxin II on skeletal muscle and on neuromuscular transmission

Effects of anemone toxin II (ATX II) have been analysed on the neuromuscular junction of the frog and different twitch muscles. Amplitudes of evoked endplate potentials and endplate currents are increased by ATX II, without effects on the amplitudes of miniature endplate potentials and endplate currents resulting from ionophoretically applied transmitter. The increase in evoked transmitter release is due to an increase in quantal content caused by an effect of the toxin on the presynaptic action potentials. ATX II is also effective on muscle fibers. The action potentials of frog twitch muscles are reversibly prolonged by ATX II. Their rate of rise and amplitudes are increased, while there is no effect on resting membrane potential. Similarly, action potentials of fast twitch muscle (extensor digitorum longus, EDL) of the mouse are reversibly prolonged by ATX II. In slow twitch muscle (soleus, SOL) of the mouse the toxin induces repetitive action potentials following the generation of a single action potential. Tetrodotoxin resistant action potentials of both denervated EDL and SOL are greatly and irreversibly prolonged by ATX II. The effects on muscle are due to a Na+ channel specific action of ATX II. Na+ current inactivation is slowed with the time constant tau h increasing towards positive membrane potentials. The steady state inactivation curve hoo was shifted to more positive potentials and its slope reduced.     

石杉碱甲对兔肌肉功能的影响和治疗实验性重症肌无力的效果

麻醉兔在体坐骨神经-腓肠肌、正中神经-旋前圆肌制备实验表明:正常兔累积iv Hup-A使腓肠肌单收缩平均增强50％的同时,功能性收缩-强直收缩平均抑制约20％,肌肉电位也受部分阻断。但对EAMG兔,iv Hup-A 25μg/kg能明显增强和改善其病态肌肉的电位和收缩功能,并能对抗d-TC所引起的阻断。     

Diazepam enhances the inhibitory action of adenosine on transmission at the frog neuromuscular junction

The effect of diazepam and its interaction with adenosine on evoked endplate potentials (e.p.p.s) and on twitch tension were investigated in innervated sartorius muscles of the frog. Diazepam (100 microM) reversibly decreased the amplitude of the e.p.p.s and the twitch responses evoked by indirect stimulation, and reversibly increased the resting membrane potential recorded from the endplates. In a concentration (30 microM) virtually devoid of an effect on the e.p.p.s, twitch responses, or resting membrane potential of the muscle fibres, diazepam potentiated the inhibitory action of adenosine on neuromuscular transmission, but not that induced by the stable analogue of adenosine 5'-N-ethylcarboxamide adenosine (NECA), which is not a substrate for the adenosine uptake system. The potentiating effect of diazepam was not observed in the presence of dipyridamole, an adenosine uptake blocker which potentiated the effect of adenosine on neuromuscular transmission. Diazepam shifted to the left the concentration-response curve obtained for adenosine in the presence of the adenosine receptor antagonist 8-phenyltheophylline (8-PT). The results suggest that diazepam acts at the frog neuromuscular junction by increasing the level of adenosine at the junction level; this increase probably results from inhibition in the uptake of the nucleoside.     

The effects of three short-acting neuromuscular blocking agents on fast- and slow-contracting muscles of the cat

The neuromuscular blocking activities of the 3 short-acting non-depolarizing agents, stercuronium, dacuronium and AH8165, were studied in the soleus and tibialis anterior muscles of the cat. In contrast to tubocurarine, both stercuronium and AH8165 produced a greater blocking action in the tibialis anterior muscle than in the soleus muscle, whereas dacuronium was equi-active in the 2 muscles. A comparison of the anticholinesterase activities of the compounds showed that there was no obvious relationship between muscle selectivity and anticholinesterase activity. It is suggested that the differing muscle selectivities of neuromuscular blocking agents may be an indication of different types of acetylcholine receptors in fast- and slow-contracting cat muscle.