Nicardipine inhibits axon conduction but causes dual changes of acetylcholine release in the mouse motor nerve

1989 ◽  
Vol 67 (12) ◽  
pp. 1493-1498 ◽  
Author(s):  
C. C. Chang ◽  
L. C. Chiou ◽  
L. L. Hwang ◽  
S. J. Hong ◽  
C. Y. Huang
Keyword(s):  
Acetylcholine Receptor ◽  
Neuromuscular Transmission ◽  
Acetylcholine Release ◽  
Motor Nerve ◽  
Neuromuscular Block ◽  
Resting Membrane Potential ◽  
Receptor Desensitization ◽  
End Plate ◽  
Agonist Action ◽  
Release Of Acetylcholine

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.

Habitual exercise enhances neuromuscular transmission efficacy of rat soleus muscle in situ

2001 ◽  
Vol 90 (3) ◽  
pp. 1041-1048 ◽  
Author(s):  
Patrice Desaulniers ◽  
Pierre-André Lavoie ◽  
Phillip F. Gardiner
Keyword(s):  
Soleus Muscle ◽  
Neuromuscular Transmission ◽  
Motor Nerve ◽  
Resting Membrane Potential ◽  
Potential Amplitude ◽  
Endplate Potential ◽  
Habitual Exercise ◽  
Rat Soleus Muscle ◽  
Miniature Endplate Potential

Rat motor nerve terminals and the endplates they interact with exhibit changes to varying patterns of use, as when exposed to increased activation in the form of endurance exercise training. The extent to which these changes affect neuromuscular transmission efficacy is uncertain. In this study, the effects of habitual exercise on the electrophysiological properties of neuromuscular transmission in rat soleus muscle were investigated using a novel in situ approach. Consistent with previous reports, miniature endplate potential frequency was enhanced by habitual exercise. Other passive properties, such as resting membrane potential, miniature endplate potential amplitude, and “giant” miniature endplate potential characteristics were unaltered by the training program. Full-size endplate potentials were obtained by blocking soleus muscle action potentials with μ-conotoxin GIIIb. Quantal content values were 91.5 and 119.9 for control and active groups, respectively ( P < 0.01). We also measured the rate and extent of endplate potential amplitude rundown during 3-s trains of continuous stimulation at 25, 50, and 75 Hz; at 50 and 75 Hz, we found both the rate and extent of rundown to be significantly attenuated (10–20%) in a specific population of cells from active rats ( P < 0.05). The results establish the degree of activity-dependent plasticity as it pertains to neuromuscular transmission in a mammalian slow-twitch muscle.

The action of sodium pump inhibitors on neuromuscular transmission

1968 ◽  
Vol 170 (1021) ◽  
pp. 381-399 ◽  
Keyword(s):  
Action Potentials ◽  
Neuromuscular Transmission ◽  
Sodium Pump ◽  
Motor Nerve ◽  
Conduction Block ◽  
Progressive Increase ◽  
Frog Skeletal Muscle ◽  
End Plate ◽  
Quantum Content ◽  
Potential Frequency

Exposure of isolated frog skeletal muscle to a cardiac glycoside produces changes in the prejunctional events associated with neuromuscular transmission. The principal changes consist of a progressive increase in the quantum content of the end-plate potential, followed by conduction block in intramuscular motor nerve branches. These events are accompanied by a progressive increase in the frequency of miniature end-plate potentials. Following conduction blockade spontaneous end-plate potentials occur which arise from the generation of action potentials at or near the nerve terminations. Still later, the miniature end-plate potential frequency declines and the nerve endings become entirely inexcitable. These changes appear to result from inhibition of a sodium pump in the motor nerve axons and their endings.

The release of acetylcholine from nerve endings by graded electric pulses

1967 ◽  
Vol 167 (1006) ◽  
pp. 23-38 ◽  
Keyword(s):  
Nerve Ending ◽  
Transmitter Release ◽  
Motor Nerve ◽  
Motor Nerve Ending ◽  
Axon Membrane ◽  
Electric Pulses ◽  
End Plate ◽  
Calcium Compound ◽  
Release Of Acetylcholine ◽  
Positively Charged

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.

Tetrodotoxin and neuromuscular transmission

1967 ◽  
Vol 167 (1006) ◽  
pp. 8-22 ◽  
Keyword(s):  
Muscle Fibre ◽  
Motor Nerve ◽  
Nerve Endings ◽  
Applied Current ◽  
End Plate ◽  
Physiological Properties ◽  
Fish Poison ◽  
Normal Frequency ◽  
Release Of Acetylcholine ◽  
Puffer Fish

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.

scholarly journals Non-quantal acetylcholine release at the neuromuscular junction

2009 ◽  
pp. 763-784
Author(s):  
F Vyskočil ◽  
AI Malomouzh ◽  
EE Nikolsky
Keyword(s):  
Skeletal Muscles ◽  
Acetylcholine Release ◽  
Chloride Transport ◽  
Motor Nerve ◽  
Basic Research ◽  
Motor Nerve Terminal ◽  
Receptor Desensitization ◽  
Quantal Acetylcholine Release ◽  
Endplate Potentials ◽  
Developing Muscle

There are two principal mechanisms of acetylcholine (ACh) release from the resting motor nerve terminal: quantal and nonquantal (NQR); the former being only a small fraction of the total, at least at rest. In the present article we summarize basic research about the NQR that is undoubtedly an important trophic factor during endplate development and in adult neuromuscular contacts. NQR helps to eliminate the polyneural innervation of developing muscle fibers, ensures higher excitability of the adult subsynaptic membrane by surplus polarization and protects the RMP from depolarization by regulating the NO cascade and chloride transport. It shortens the endplate potentials by promoting postsynaptic receptor desensitization when AChE is inhibited during anti-AChE poisoning. In adult synapses, it can also activate the electrogenic Na+/K+-pump, change the degree of synchronization of quanta released by the nerve stimulation and affects the contractility of skeletal muscles.

scholarly journals SIZES OF END PLATE COMPARTMENTS, DENSITIES OF ACETYLCHOLINE RECEPTOR AND OTHER QUANTITATIVE ASPECTS OF NEUROMUSCULAR TRANSMISSION

1973 ◽  
Vol 21 (9) ◽  
pp. 769-778 ◽  
Author(s):  
MIRIAM M. SALPETER ◽  
MOHYEE E. ELDEFRAWI
Keyword(s):  
Surface Area ◽  
Acetylcholine Receptor ◽  
Neuromuscular Transmission ◽  
Nerve Impulse ◽  
Synaptic Cleft ◽  
Postsynaptic Membrane ◽  
Optimal Response ◽  
End Plate

The area of the postsynaptic membrane and the volume of the synaptic cleft were calculated for the end plates of the diaphragm and sternomastoid of mouse and rat. From these dimensions we were able to extrapolate, from data given by others on acetylcholine (ACh) released during neuromuscular transmission and on ACh receptor per whole end plate, to densities in the postneural compartments. The concentration of ACh in the cleft per nerve impulse was found to be ~ 10–5 M and the density of ACh receptor was between 5 and 10 x l03/µ2 of postsynaptic membrane. (This is approximately a factor of 2 to 3 higher than that for acetylcholinesterase at this site.) From these values we conclude that the concentration of ACh receptor in the plane of the postsynaptic membrane is considerably higher than that of ACh in the cleft during neuromuscular transmission. In addition the ACh itself is present at considerably higher concentrations than necessary to give optimal response. We calculated that the acytelcholinesterase plus ACh receptor together would occupy about 25% of the surface area of the postsynaptic membrane.

The effect of calcium on acetylcholine release from motor nerve terminals

1965 ◽  
Vol 161 (985) ◽  
pp. 496-503 ◽  
Keyword(s):  
Neuromuscular Junction ◽  
Calcium Ions ◽  
Acetylcholine Release ◽  
Motor Nerve ◽  
Nerve Terminals ◽  
Transmission Process ◽  
Terminal Axon ◽  
Deficient Medium ◽  
Site Of Action ◽  
Release Of Acetylcholine

The method of external focal recording from the neuromuscular junction has been used to locate the site of action of calcium ions in the transmission process. The muscle is placed in a calcium-deficient medium (which contains magnesium as a substitute), and the effect of localized calcium application from the recording micropipette is studied. Electrophoretic application of calcium is followed within less than 1 s by increased terminal release of acetylcholine, shown by a large increase in the number of quantal components of the end-plate potential. This effect is observed even under conditions when the terminal axon spike diminishes in size during the application of calcium. It is concluded that the action of calcium is concerned directly with the release of the transmitter, and not indirectly—as is sometimes suggested—by facilitating propagation or increasing the amplitude of the terminal nerve spike.

Action of Tetraethylammonium Chloride on Neuromuscular Transmission in Frogs

1958 ◽  
Vol 193 (1) ◽  
pp. 213-218 ◽  
Author(s):  
Kyozo Koketsu
Keyword(s):  
Action Potential ◽  
Neuromuscular Transmission ◽  
Direct Action ◽  
Motor Nerve ◽  
Muscle Fibers ◽  
Nerve Fibers ◽  
Tetraethylammonium Chloride ◽  
Nerve Axon ◽  
Mechanical Responses ◽  
End Plate

The action of tetraethylammonium chloride (TEA-Cl) on the neuromuscular transmission in frogs of 0.2–3 mm concentration was analyzed by recording a) the mechanical responses; b) direct action on the muscle fibers; c) end-plate potential (e.p.p.); d) direct action on the end-plate membrane; e) sensitivity of end-plate membrane to the applied ACh; f) the action potential of terminal endings of motor nerve fibers; g) direct action of nerve axon. TEA-Cl in these concentrations augments the e.p.p., and this augmentation increases with increasing concentrations. A relatively higher concentration (1–3 mm) depresses the e.p.p. after an initial augmentation. The sensitivity of the end-plate membrane to ACh is depressed by 0.2–3 mm. TEA-Cl in these concentrations acts on the terminal endings of motor nerve fibers and prolongs the negative after-potential of terminal endings. It is suggested that TEA-Cl increases the release of ACh by acting on the terminal endings, thus causing the augmentation of e.p.p.'s. The action of TEA-Cl at a given concentration will be determined by separate actions both on the end-plate membrane and the terminal ending of motor nerve fibers.

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