A pharmacological study of the effect of carbamazepine on neuromuscular transmission in the rat diaphragm

The effects of carbamazepine (0.042-0.42 mM) on neuromuscular transmission were studied on the isolated rat phrenic nerve diaphragm preparation using standard pharmacological and electrophysiological methods. Carbamazepine decreased (1) the antidromic activity of the phrenic nerve, (2) the amplitude of the endplate potential (EPP) and miniature endplate potential (MEPP), (3) the quantal content of the endplate potential, (4) the indirectly-elicited twitch tension, (5) the muscle contracture in chronically denervated muscle induced by acetylcholine (ACh) and (6) the amplitude of the compound phrenic nerve action potential, in a concentration-dependent manner. The antidromic activity of the phrenic nerve was the most affected, while the phrenic nerve compound action potential was least affected. However, the IC50 for carbamazepine (the concentration of carbamazepine that inhibited 50% of the response) was in the same order of concentration, i.e. 0.11-0.3 mM. Compared with the effect of carbamazepine on the indirectly-elicited twitch tension with its actions described above, it is concluded that carbamazepine interfered with the neuromuscular activity by inhibiting pre- and postsynaptic process and conduction in the phrenic nerve.     

The effect of carbamazepine on the post-tetanic twitch tension in the diaphragm of the mouse

The effects of carbamazepine (0.084-0.25 mM) on the post-tetanic potentiation of the twitch tension, were studied on the isolated phrenic nerve diaphragm preparation of the mouse. Carbamazepine decreased the post-tetanic potentiation of the twitch tension. The maximal depressant effect was found after higher frequencies and longer durations of stimulation. After repetitive stimulation, the amplitude of the endplate potential and the frequency of miniature endplate potentials were potentiated. Carbamazepine decreased the post-tetanic potentiation of the amplitude of endplate potential and the frequency of miniature endplate potentials. The directly-elicited muscle action potential was not affected when post-tetanic potentiation of the twitch tension was decreased. It is concluded that carbamazepine suppressed the post-tetanic potentiation of the indirectly-elicited twitch tension, mainly due to its pre-synaptic inhibitory effect.     

Inhibition by local anaesthetic drugs at low and high stimulation frequencies: A comparison between the isolated phrenic nerve of the rat and the phrenic nerve-diaphragm preparation

The effects of lidocaine (0.25 mM), prilocaine (0.3 mM), diphenylhydantoin (0.24 mM), tetraeaine (0.005 mM) and dibucaine (0.002 mM) on the isolated rat phrenic nerve, neuromuseular transmission and the directly stimulated rat diaphragm, were observed at low (twitch) and high (tetanic) stimulation frequency. The phrenic nerve compound action potential and muscle tension during indirect and direct stimulation were compared.At high frequency stimulation all drugs caused high frequency inhibition of both nerve and muscle. The high frequency inhibition was usually biphasic with an initial decrease in the amplitude of compound action potential and tetanic tension and a subsequent stabilization at a reduced plateau level. The duration of the initial phase increased with the potency of the drugs and was similar for nerve and muscle. A specific high frequency inhibition during indirect stimulation was found with diphenylhydantoin and prilocaine, indicating pre- and post-synaptic inhibition of neuromuscular transmission.At low frequency stimulation, the drugs induced a basal inhibition of the nerve compound action potential. In spite of that, the twitches were not depressed during indirect stimulation of the muscle, illustrating the margin of safety with neuromuscular transmission.These results indicate that the action of the drug was similar at the excitable nerve and muscle membranes when stimulated at high frequency, but different at low frequency stimulation.     

Reduction of quantal size and inhibition of neuromuscular transmission by bafilomycin A

The energy for uphill transport of neurotransmitters into synaptic vesicles is created by bafilomycin A- and concanamycin A-sensitive vacuolar H(+)-ATPase (V-ATPase). Both blockers (at 0.1-5 microM) depressed twitch tension and induced tetanic fade of mouse diaphragm on stimulation of the phrenic nerve. Axonal impulse conduction and depolarization of motor endplate by exogenous acetylcholine were not inhibited. The IC(50)s for bafilomycin A and concanamycin A were 1.1+/-0.2 and 0.7+/-0.1 microM, respectively. Contractile response evoked by stimulation of diaphragm, muscle resting membrane potential and membrane resistance were not altered. V-ATPase blockers decreased quantal size and shifted the distribution of miniature endplate potentials (mepps) to low amplitude direction. The increase of mepp events in high KCl medium was suppressed slightly. The blockers depressed endplate potentials (epps) with IC(50)s of 0.7+/-0.2 microM (bafilomycin A) and 0.4+/-0.1 microM (concanamycin A). On high frequency stimulation, the coefficient of variance and run-down of epps were increased. The inhibitory effects on mepps and epps were irreversible and augmented by nerve stimulation. The results suggest that inhibition of V-ATPase reduces the acetylcholine content of synaptic vesicles, leading to suppression of neuromuscular transmission.     

吡喹酮对神经肌肉接头传递的作用

吡喹酮可使电刺激腓总神经所引起的胫前肌收缩反应明显加强。如给腓总神经施加超强刺激,静脉注射筒箭毒碱可减弱肌肉收缩反应,吡喹酮却能加强筒箭毒碱的抑制作用,使神经肌肉传递迅即完全阻断。采用微电极细胞内记录技术研究吡喹酮对离体大鼠膈神经隔肌的作用,发现吡喹酮不明显影响膈肌细胞的静息膜电位。低浓度吡喹酮(2×10^-4M)可使微终板电位(mepp)频率明显增加。高浓度吡喹酮8×10^-4M则使mepp振幅逐渐变小和消失。吡喹酮在使神经肌肉传递阻滞不断加深的同时,尚能使终板电位的振幅变小,终致完全消失。     

Effects of memantine on the twitch tension of mouse diaphragm

The effects of memantine (50-175 microM) on the post-tetanic potentiation of the twitch tension were studied on the isolated mouse nerve diaphragm preparation. Memantine completely abolished the twitch tension elicited indirectly while it had no effect on the directly elicited twitch tension. Memantine also decreased the post-tetanic potentiation of amplitude of endplate potential and twitch tension. The duration of tetanic stimulation that induced a maximal decrease of twitch tension was 10-20 s. It is suggested that the effect of memantine on post-tetanic potentiation may be due to its voltage- and time-dependent effect on the ion channel-acetylcholine receptor complex.     

Neuromuscular blocking profile of the vecuronium analogue, Org-9487, in the rat isolated hemidiaphragm preparation.

1. The neuromuscular effects of the short-acting aminosteroid muscle relaxant Org-9487 have been studied in the in vitro rat phrenic nerve/hemidiaphragm preparation by use of twitch tension and electrophysiological recording techniques. 2. Org-9487 (5-100 microM) produced a concentration-dependent decrease in the amplitude of twitches (0.1 Hz) and tetanic contractions (50 Hz) evoked by motor nerve stimulation. The compound produced fade of force during both 50 Hz stimulation and train-of-four stimulation at 2 Hz, indicating a prejunctional component of action. 3. Anticholinesterases only partially reversed the effect of Org-9487 on twitch responses. This was possibly because, at the concentrations required to block twitches in the rat, Org-9487 itself was found to possess significant anticholinesterase activity. 4. Org-9487 (3 microM) increased the rundown of endplate current amplitudes during a 2 s train of 50 Hz nerve stimulation. This was because Org-9487 increased the quantal content of the first endplate current in the train without affecting acetylcholine release towards the latter part of the train. 5. Org-9487 (10 microM) produced a voltage-dependent decrease in the time constant of decay of endplate currents at 32 degrees C and 0.5 Hz, indicative of a block of endplate ion channels. The blocking rate constant increased with membrane hyperpolarization.     

Muscle paralyzing effect of the juice from the trunk of the banana tree

Y. N. Sinsgh and W. F. Dryden. Muscle paralyzing effect of the juice from the trunk of the banana tree. Toxicon23, 973–981, 1985. — The effect of an extract from the trunk of the banana tree (Musa sapientum) was investigated in isolated skeletal muscle preparations from the chick, mouse and frog using twitch tension and intracellular recording techniques. The extract produced, in the same concentration range and after an initial period of twitch augmentation, paralysis of skeletal muscle in both directly and indirectly stimulated preparations. It also had a dosedependent stimulant effect on the muscle causing a contracture. The neuromuscular blockade was reversed by calcium, but only when added before complete paralysis of the muscle. On the other hand, neostigmine usually hastened the blockade and aggravated the contracture. The frequency of the miniature endplate potential in the mouse phrenic nerve — diaphragm preparation greatly increased initially, declining to an elevated plateau. Effects on quantal content of endplate potentials e.p.p.s were studied in the transected mouse phrenic nerve — hemidiaphragm using trains of e.p.p.s. In the presence of the extract, only a few e.p.p. trains could normally be evoked, probably due to nerve terminal block. When quantal content could be measured at low concentrations of the extract, an increase was usually obtained. Muscle action potentials in the frog sartorius muscle were decreased in amplitude until no further potentials could be generated. The results suggest that the nature of the block produced by the extract resembles that of a potent local anaesthetic with an initial atypical labilizing effect on cell calcium rather than a conventional curariform block.     

A further study of the neuromuscular effects of vesamicol (AH5183) and of its enantiomer specificity.

1. The effects of vesamicol (2-(4-phenylpiperidino) cyclohexanol), an inhibitor of acetylcholine storage, and its two optical isomers have been studied on neuromuscular transmission in rat and frog muscle, and on nerve conduction in frog nerve. 2. Racemic vesamicol produced a pre-block augmentation of twitch tension that also occurred in directly-stimulated muscle. This effect is thus at least partially due to an increase in muscle contractility. 3. (-)-Vesamicol was approximately 20 times more potent than (+)-vesamicol in blocking twitches elicited at 1 Hz. This degree of stereoselectivity is similar to that measured for inhibition of acetylcholine uptake by isolated synaptic vesicles. Both enantiomers were equally weak in reducing nerve action potential amplitude in frog nerve. 4. Further studies with the active isomer, (-)-vesamicol, showed that, like that produced by racemic vesamicol, the neuromuscular block was highly frequency-dependent. The block was not reversed by choline or neostigmine, but was partially reversed by 4- or 3,4-aminopyridine. 5. Preliminary electrophysiological studies showed that vesamicol reduced miniature endplate potential amplitude in rapidly-stimulated frog nerve-muscle preparations. Addition of lanthanum ions increased the frequency of miniature endplate potentials and led to the appearance of apparently normal-sized potentials amongst those of reduced amplitude. 6. The results show the close agreement between pharmacological and biochemical observations indicating the suitability of the rat diaphragm as a test model for substances of this nature. The degree of reversibility of the vesamicol-induced neuromuscular block by aminopyridines was unexpected, and it is suggested that in the presence of a drug which greatly increases release, a pool of acetylcholine is capable of being released which is not normally releasable after block of storage by vesamicol. It is also considered possible that the results from the intracellular recording studies may be explained in these terms.     

Pumiliotoxin-C and synthetic analogues. A new class of nicotinic antagonists

Pumiliotoxin-C (PTX-CI), a cis-decahydroquinoline alkaloid, and synthetic analogues inhibited directly and indirectly elicited twitches in rat phrenic nerve diaphragm preparations. At 40 microM the most potent analogue, 2,5-di-n-propyl-cis-decahydroquinoline (PTX-CII), reversibly blocked the indirectly elicited twitch and markedly depressed the amplitude of end-plate potentials and miniature end-plate potentials without affecting muscle membrane potential. PTX-CII did not depress the directly elicited twitch in diaphragm muscle treated with alpha-bungarotoxin. At 40 microM, the compound blocked extrajunctional acetylcholine (ACh) sensitivity in chronically denervated soleus muscle of the rat. The peak amplitude of the end-plate current in frog sartorius muscle was depressed by PTX-CII at both positive and negative membrane potentials. Nonlinearity in the current-voltage relationship appeared at membrane potentials greater than -100 mV with concentrations of PTX-CII from 2.5 to 7.5 microM. The decay phase of the end-plate current was shifted to lower values such that it decayed faster at all membrane potentials but retained voltage sensitivity. PTX-CII, the most potent of the analogues, inhibited binding of [3H]perhydrohistrionicotoxin to Torpedo electroplax membranes with an IC50 value of 1.5 microM in the absence of carbamylcholine (Carb) and 0.1 microM in the presence of Carb. The other analogues were less potent, but all showed higher affinities in the presence of Carb. PTX-CI, PTX-CII, and PTX-CIII had no effect on the binding of [125I]alpha-bungarotoxin to ACh receptors in Torpedo membranes while slightly enhancing the binding of [3H]ACh, whereas PTX-CIV gave slight inhibition of both receptor ligands at concentrations greater than 10 microM. The pumiliotoxin-C class of alkaloids therefore appears to block neuromuscular transmission primarily via interactions with sites associated with the ion channel controlled by the ACh receptor.     

Effects of sodium selenite on neuromuscular junction of the mouse phrenic nerve-diaphragm preparation

The effects of sodium selenite on the neuromuscular junction of the phrenic nerve-diaphragm of the mouse were studied. Nerve-evoked twitches of the diaphragm of the mouse, the frequency of miniature endplate potentials, the quantal content of endplate potentials and the compound action potentials of the axon were measured. Sodium selenite induced a slight increase of the amplitude of the twitch, followed by twitch depression. The amplitude of the twitch, increased by selenite, became more prominent after the suppression of the twitch induced by cadmium ions, d-tubocurarine or magnesium ions. It appeared that the increased amplitude of twitch was due to the facilitation of transmitter release, since selenite significantly increased the frequency of miniature endplate potentials, and the amplitude and quantal content of endplate potentials; the amplitude and half decay time of miniature endplate potentials were unaffected. Twitch depression induced by selenite was enhanced by ammonium ions, high potassium and low magnesium and attenuated by high calcium. During the period of gradual depression of the twitch, selenite decreased the amplitude of compound action potentials of the phrenic nerve axon and caused the disappearance of endplate potentials. Ammonium ions enhanced the blockade of axonal conduction induced by selenite. Moreover, the depolarizing agents, ammonium and high potassium also induced an initial increase of twitch amplitude followed by depression of the twitch. These findings indicate that selenite probably alters the release of the transmitter by depolarizing the nerve membrane. The effects of selenite were antagonized by glutathione and cyanide, suggesting that the binding of selenite to sulfhydryl groups of the membrane was essential for inducing its pharmacological actions.     

Effects of diacetyl monoxime on neuromuscular transmission

The action of diacetyl monoxime on neuromuscular transmission has been studied in frogs, chickens, and cats, and in isolated rat phrenic nerve-diaphragm preparations. In frogs and chickens the oxime caused a flaccid paralysis; in chickens there was sometimes opisthotonos. In the indirectly stimulated rat diaphragm, diacetyl monoxime decreased the height of a single twitch, but a tetanus was well sustained. In cats, the twitch height of the indirectly excited gastrocnemius-soleus muscle was reduced by diacetyl monoxime more than was that of the tibialis anterior muscle, but in both muscles a tetanus was well maintained. Diacetyl monoxime reduced the response to direct stimulation of both the rat diaphragm and cat muscles. Diacetyl monoxime injected intra-arterially in the cat elicited a transient hypertension and a gasp. Diacetyl monoxime did not reverse the neuromuscular block caused by anticholinesterases either in isolated rat phrenic nerve-diaphragm preparations or in cats.     

Mode of neuromuscular blocking action of a toxic phospholipase A2 from Pseudocerastes fieldi (Field's horned viper) snake venom

The effects of a toxic phospholipase A2 (Fr.Cb) isolated from the venom of Pseudocerastes fieldi were studied on the chick biventer cervicis muscle and the mouse phrenic nerve--diaphragm preparations. In the chick muscle, Fr.Cb (10 micrograms/ml) caused complete neuromuscular blockade without producing contracture or affecting the response of the muscle to acetylcholine. In the mouse diaphragm, Fr.Cb blocked the indirectly elicited contraction without affecting that evoked directly. In a low calcium medium (0.5 mM), Fr.Cb produced a triphasic change of the indirectly elicited contractions. The frequency of miniature endplate potentials (m.e.p.p.s) in the mouse diaphragm was first increased 3--4 fold 40 min after toxin (10 micrograms/ml) application, then gradually decreased, while the amplitude of m.e.p.p.s. was not decreased, even after the evoked release of transmitter had failed. Giant m.e.p.p.s were frequently observed. The quantal content first increased and then decreased gradually. The resting membrane potential and the compound phrenic nerve action potential were not significantly affected by the toxin at 10 micrograms/ml after 2 hr of incubation. The motor nerve terminals in the Fr.Cb intoxicated mouse diaphragm showed swelling and vacuolization of both synaptic vesicles and mitochondria. It is concluded that the toxin produces a neuromuscular blockade by acting selectively on the presynaptic site.     

Effects of non-sedative anxiolytic drugs on responses to GABA and on diazepam-induced enhancement of these responses on mouse neurones in cell culture.

1. The effects of adenosine and adenosine analogues 2-chloroadenosine (CADO), L-N6-phenylisopropyladenosine (L-PIA), D-N6-phenylisopropyladenosine (D-PIA), N6-cyclohexyladenosine (CHA) and 5'-N-ethylcarboxamide adenosine (NECA) on evoked endplate potentials (e.p.ps) and on twitch tension were investigated in innervated diaphragms of the rat. 2. Adenosine and its analogues decreased, in a concentration-dependent manner, the amplitude of both the e.p.ps and the twitch responses evoked by nerve stimulation. The order of potency in decreasing the twitch tension was CHA, L-PIA, NECA greater than D-PIA greater than CADO greater than adenosine. L-PIA was about 8 times more potent than D-PIA. Neither adenosine nor the adenosine analogues affected the twitch responses of directly stimulated tubocurarine-paralysed muscles. 3. 8-Phenyltheophylline (8-PT), theophylline and isobutylmethylxanthine (IBMX), in concentrations virtually devoid of effect on neuromuscular transmission, antagonized the inhibitory effect of 2-chloroadenosine. The order of potency of the alkylxanthines as antagonists of the adenosine receptor at the rat diaphragm neuromuscular junction was 8-PT greater than IBMX greater than theophylline. The antagonism by these xanthines was shown to be competitive, the pA2 value for 8-PT being 7.16. In concentrations slightly higher than those used to test its ability to antagonize the adenosine receptor, IBMX and 8-PT increased the amplitude of e.p.ps without modifying their decay phase or the resting membrane potential of the muscle fibre. 4. The adenosine uptake inhibitor, nitrobenzylthioinosine (NBI) and the adenosine deaminase inhibitor, erythro-9(2-hydroxy-3-nonyl)adenine (EHNA), in concentrations virtually devoid of effect on neuromuscular transmission, potentiated the inhibitory effect of adenosine at the rat diaphragm neuromuscular junction. The potentiation factors were about 2.6 for NBI (5 microM), 2.2 for EHNA (25 microM) and 4.6 for the combination of NBI (5 microM) and EHNA (25 microM). 5. It is concluded that both uptake and deamination contribute to the inactivation of adenosine at the rat diaphragm neuromuscular junction and that in this preparation the inhibitory effect of adenosine on transmission is mediated by a xanthine-sensitive adenosine receptor with an agonist profile which does not fit the criteria for its classification either as an A1 or A2-adenosine receptor.     

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.     

Antagonism by beta-eudesmol of neostigmine-induced neuromuscular failure in mouse diaphragms.

beta-Eudesmol, a sesquiterpenol extracted from a Chinese herb, Atractylodes lancea, at 10-80 microM, did not affect muscle action potentials, miniature and evoked endplate potentials and acetylcholine-induced depolarization in the presence or absence of neostigmine in mouse phrenic nerve-diaphragms. However, the tetanic fade, muscle fasciculation and twitch potentiation induced by neostigmine were effectively antagonized by 20 microM beta-eudesmol. When trains of pulses were applied to the nerve in the presence of neostigmine, beta-eudesmol reduced the incidence of explosive depolarization of the endplate from 95% to 35-67% of junctions, and shortened the duration when it occurred. Moreover, both the maximal and steady-state depolarizations during repetitive stimulation were reduced while the amplitudes of steady-state endplate potentials were increased. The results suggest that beta-eudesmol antagonized neostigmine-induced neuromuscular failure mainly by a presynaptic action to depress the regenerative release of acetylcholine during repetitive stimulation. The mechanism of antagonism is obviously not tubocurarine-like and it is unrelated to desensitization of acetylcholine channels.     

Inhibition of neuromuscular transmission in isolated mouse phrenic nerve-diaphragm by the enterotoxin of Clostridium perfringens type A.

The enterotoxin of Clostridium perfringens type A, a channel forming protein toxin, inhibited neuromuscular transmission under conditions of low calcium. Twitch tension of isolated phrenic nerve-diaphragm preparations elicited by electrical stimulations to the phrenic nerve was recorded isometrically, and the preparations were exposed to the purified enterotoxin. In Krebs solution containing 0.5 mM calcium, the enterotoxin (20 micrograms/ml) reduced within 10 min the amplitude of the twitch tension to 34 +/- 7% (mean +/- S.D., n = 11) of that recorded before the treatment. The effects of the enterotoxin on the twitch tension were irreversible and proceeded independently of stimulation. The reduction of the twitch tension by the enterotoxin was apparent in Krebs solution containing less than 0.6 mM calcium and the degree of reduction was inversely related to the concentration of calcium. The reduction of the twitch tension by the enterotoxin was also dependent on temperature and concentration of the toxin. At temperatures below 20 degrees C, no obvious reduction of twitch tension was observed with 20 micrograms/ml of the enterotoxin. Enterotoxin at a concentration of 0.4 micrograms/ml caused 16 +/- 2% (mean +/- S.D., n = 4) reduction of twitch tension, and the degree of the reduction in twitch tension increased with toxin concentration, reaching a plateau of 65 +/- 4% (mean +/- S.D., n = 7) at 6.5 micrograms/ml of the enterotoxin. The effects of the enterotoxin were antagonized by 2 microM physostigmine. Unlike curare, pretreatment of the preparation with enterotoxin did not antagonize the neuromuscular block by decamethonium. Neither the tension of muscular twitch elicited by direct electrical stimulation to the muscle nor the resting membrane potentials of muscle fibers recorded intracellularly were affected by the enterotoxin. The enterotoxin (2.2 micrograms/ml) reduced the frequency, but not mean amplitude or amplitude distribution, of miniature end-plate potentials, from 0.91 +/- 0.07/sec to 0.72 +/- 0.07 (mean +/- S.E., n = 5). The results suggest that the enterotoxin will provide a novel tool for the studies on the mechanism of the neuromuscular transmission because of the unique characteristics of the inhibition and of the known mechanism of its action on the cell membrane.     

Pharmacological aspects of neuromuscular transmission in the isolated diaphragm of the dystrophic (Rej 129) mouse.

1. Some aspects of the pharmacology of neuromuscular transmission have been studied in the isolated diaphragm of the normal and dystrophic mouse. 2. The effects of (+)-tubocurarine and atropine on the indirectly elicited twitch responses of the dystrophic diaphragm were indistinguishable from normal. 3. Intracellular recording techniques revealed no significant differences between the rise time, time to half decay, frequency and amplitude of miniature endplate potentials (m.e.p.ps) recorded in dystrophic muscle fibres, compared to those recorded in normal muscle fibres. 4. Transmitter null potential, the size of the available store of transmitter, the probability of release of the transmitter, and the characteristics of endplate potentials (e.p.ps) of dystrophic muscle fibres did not differ from normal. 5. The quantum contents of e.p.ps generated in response to nerve stimulation of 0.1 to 100 HZ were consistently larger in dystrophic muscle fibres than in normal muscle fibres, but the differences were not statistically significant under the conditions of the experiment.     

Relative potencies of metal ions on transmitter release at mouse motor nerve terminals.

1. The effects of a range of metal ions were systematically studied at the mouse neuromuscular junction in order to investigate the type of calcium channel present at the nerve terminal. 2. Endplate potentials and miniature endplate potentials were recorded from the phrenic nerve diaphragm muscle preparation with glass microelectrodes. 3. Endplate potential amplitudes and quantal contents were reduced by manganese (IC50 220 microM), cadmium (IC50 11 microM), cobalt (IC50 350 microM), and nickel (IC50 420 microM). Miniature endplate potentials were not affected by these ions at concentrations equal to the IC50s. Gadolinium did not reduce endplate potentials up to 100 microM. 4. Comparisons made with known channel types in neuroblastoma cell lines suggest that the calcium channels at the motor nerve terminal are different from those types studied in the cell lines, although most similarity is shown to the high-voltage activated calcium channel types.