Tetrodotoxin and neuromuscular transmission

1. The puffer fish poison, tetrodotoxin ( T . T .) was applied to eliminate impulse propagation in nerve and muscle fibre, and the physiological properties of the neuromuscular junction were studied under this condition. 2. Spontaneous miniature end-plate potentials of normal frequency and amplitude were recorded in the T . T .-paralysed muscle. 3. Depolarization of motor nerve endings by locally applied current still produces the usual increase in the frequency of miniature end-plate potentials (e. p. ps). 4. When brief current pulses are applied to the nerve endings e. p. ps can be evoked, whose size varies with the intensity of the current. The responses are composed, like normal e. p. ps, of a statistically varying number of miniature potentials. The response fails when calcium is removed from the bath. 5. When two identical pulses are applied at varying intervals, facilitation of the second e. p. p. occurs, similar to that observed normally with pairs of nerve impulses. 6. It is concluded that tetrodotoxin while blocking electric excitation in nerve and muscle does not interfere with the release of acetylcholine from nerve endings nor with its local action on the muscle fibre.

1. The effect of brief depolarizations focally applied to a motor nerve ending was studied. Particular attention was paid to the relation between (i) strength and duration of the pulse and (ii) the size and latency of the resulting end-plate potential. 2. The release of acetylcholine lags behind the depolarization which causes it. If pulses of less than 4 ms duration are used (at 5 °C), the release starts after the end of the pulse. 3. Within a certain range, lengthening the pulse increases the rate of the ensuing transmitter release. 4. Unexpectedly, lengthening the depolarizing pulse also increases the latency of the transmitter release. This finding is discussed in detail. It is regarded as evidence suggesting that entry into the axon membrane of a positively charged substance (external Ca 2+ ions or a calcium compound Ca R + ) is the first step leading to the release of acetylcholine packets from the terminal.


1989 ◽  
Vol 67 (12) ◽  
pp. 1493-1498 ◽  
Author(s):  
C. C. Chang ◽  
L. C. Chiou ◽  
L. L. Hwang ◽  
S. J. Hong ◽  
C. Y. Huang

The effects of nicardipine, a dihydropyridine Ca2+-channel antagonist, on neuromuscular transmission and impulse-evoked release of acetylcholine were compared with those of nifedipine. In the isolated mouse phrenic nerve diaphragm, nicardipine (50 μM), but not nifedipine (100 μM), induced neuromuscular block, fade of tetanic contraction, and dropout or all-or-none block of end-plate potentials. Nicardipine had no significant effect on the resting membrane potential and the amplitude of miniature end-plate potentials but increased the frequency and caused the appearance of large size miniature potentials. The quantal contents of evoked end-plate potentials were increased. In the presence of tubocurarine, however, nicardipine depressed the amplitude of end-plate potentials. The compound nerve action potential was also decreased. It is concluded that nicardipine blocks neuromuscular transmission by acting on Na+ channels and inhibits axonal conduction. Nicardipine appeared to affect the evoked release of acetylcholine by dual mechanisms, i.e., an enhancement presumably by an agonist action on Ca2+ channels, like Bay K 8644 and nifedipine, and inhibition by an effect on Na+ channels, like verapamil and diltiazem. In contrast with its inactivity on the amplitude of miniature end-plate potentials, depolarization of the end plate in response to succinylcholine was greatly depressed. The contractile response of baby chick biventer cervicis muscle to exogenous acetylcholine was noncompetitively antagonized by nicardipine (10 μM), but was unaffected by nifedipine (30 μM). These results may implicate that nicardipine blocks the postsynaptic acetylcholine receptor channel by enhancing receptor desensitization or by a use-dependent effect.Key words: nicardipine, calcium channel antagonists, neuromuscular transmission, acetylcholine release, acetylcholine receptor desensitization.


1936 ◽  
Vol 86 (4) ◽  
pp. 353-380 ◽  
Author(s):  
H. H. Dale ◽  
W. Feldberg ◽  
M. Vogt

At the nerve-muscle junction, a specific process occurs which is not found during the propagation of impulses along nerve or muscle fibres; the nerve impulse causes acetylcholine (Ach) to be released from the motor nerve endings, and this substance depolarizes the end-plate surface of the muscle fibre by a specific chemical reaction. The transient local depolarization of the muscle fibre which is so produced has been called the end-plate potential (e.p.p.). The e.p.p., then, unlike the nerve or muscle impulse, is not itself produced by electric stimulation (direct spread of electric current from nerve to muscle has, in fact, never been demonstrated and appears to be indetectably small). On the other hand, the e.p.p. electrically stimulates the surrounding region of the muscle fibre, and so gives rise to the propagation of a new impulse.


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