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.

Influence of presynaptic receptors on neuromuscular transmission in rat

1982 ◽  
Vol 242 (5) ◽  
pp. C366-C372 ◽  
Author(s):  
D. F. Wilson
Keyword(s):  
Transmitter Release ◽  
Action Potentials ◽  
Physiological Function ◽  
Motor Nerve ◽  
Presynaptic Receptors ◽  
End Plate ◽  
Feedback Pathway ◽  
Partial Blockade ◽  
Ach Receptors

The presence and physiological significance of acetylcholine (ACh) receptors on motor nerve terminals was examined at the rat diaphragm neuromuscular junction. Intracellular recording techniques were used to monitor end-plate potentials (EPP), miniature end-plate potentials (MEPP), and resting potentials of the muscle fibers. Muscle action potentials were blocked by the cut-muscle technique. Quantal release was determined by the ratio EPP/MEPP, after correcting for nonlinear summation. Blockade of acetylcholinesterase with eserine and neostigmine was tested to determine the influence of residual ACh on transmitter release. Partial blockade of ACh receptors with curare was examined to further clarify the role of these presynaptic receptors. The experiments demonstrate that residual ACh inhibits transmitter release and that blockade of ACh receptors enhances transmitter release. It is concluded that presynaptic ACh receptors exist and that they serve an important physiological function. It is suggested that the presynaptic ACh receptors normally serve to limit transmitter release in a negative feedback pathway.

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.

Age-associated changes in neuromuscular transmission in the rat

1984 ◽  
Vol 247 (3) ◽  
pp. C288-C292 ◽  
Author(s):  
D. F. Wilson ◽  
R. C. Cardaman
Keyword(s):  
Neuromuscular Junction ◽  
Action Potentials ◽  
Neuromuscular Transmission ◽  
Age Groups ◽  
Physiological Changes ◽  
Muscle Action ◽  
Rat Diaphragm ◽  
Statistical Probability ◽  
End Plate ◽  
Old Rats

The physiological changes in neuromuscular transmission associated with age were examined in rats between the ages of 1 mo (28 days) and 1 yr (364 days). Intracellular recording techniques were used to monitor end-plate potentials and miniature end-plate potentials at the rat diaphragm neuromuscular junction. Muscle action potentials were blocked by cutting the muscle fibers. Neuromuscular transmission was significantly different in 28-day-old rats compared with the older rats (42-364 days). The 28-day-old rats released fewer quanta. The statistical store in the immature rats was also significantly smaller than in the older age groups. The statistical probability of release, however, was not significantly different from the older animals. Examination of the presynaptic parameters in rats between the ages of 42 and 364 days revealed no significant increases in quantal release. It is concluded that the neuromuscular junction matures physiologically by 6 wk of age in rats and remains stable through the 1st yr of life.

POSTSYNAPTIC EFFECTS OF HC-3 AT THE NEUROMUSCULAR JUNCTION OF THE FROG

1961 ◽  
Vol 39 (2) ◽  
pp. 343-349 ◽  
Author(s):  
A. R. Martin ◽  
R. K. Orkand
Keyword(s):  
Neuromuscular Junction ◽  
Intracellular Recording ◽  
Neuromuscular Transmission ◽  
Muscle Fibers ◽  
Marked Change ◽  
Single Muscle ◽  
End Plate ◽  
Quantum Content ◽  
Iontophoretic Application

Intracellular recording from single muscle fibers has been used to study the effects of hemicholinium No. 3 (HC-3) on neuromuscular transmission in the excised m. ext. l. dig. IV of the frog. Concentrations of HC-3 greater than 10−5 M decreased the amplitude of the end-plate potentials (e.p.p.'s) and the magnitude of the depolarization produced by iontophoretic application of acetylcholine. Neither a decrease in e.p.p. quantum content nor depolarization of the end plate accompanied the decreased e.p.p. amplitude. The duration of the potential produced by the application of ACh was increased and the falling phase of the e.p.p. prolonged. 10−4 M HC-3 produced a marked change in the shape of the e.p.p., the effect being similar to that produced by procaine.

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.

Calcium-dependent potassium conductance in rat supraoptic nucleus neurosecretory neurons

1985 ◽  
Vol 54 (6) ◽  
pp. 1375-1382 ◽  
Author(s):  
C. W. Bourque ◽  
J. C. Randle ◽  
L. P. Renaud
Keyword(s):  
Time Constant ◽  
Action Potentials ◽  
Supraoptic Nucleus ◽  
Potassium Conductance ◽  
Reversal Potential ◽  
Input Resistance ◽  
Mean Amplitude ◽  
Progressive Increase ◽  
Calcium Dependent ◽  
Neurosecretory Neurons

Intracellular recordings of rat supraoptic nucleus neurons were obtained from perfused hypothalamic explants. Individual action potentials were followed by hyperpolarizing afterpotentials (HAPs) having a mean amplitude of -7.4 +/- 0.8 mV (SD). The decay of the HAP was approximated by a single exponential function having a mean time constant of 17.5 +/- 6.1 ms. This considerably exceeded the cell time constant of the same neurons (9.5 +/- 0.8 ms), thus indicating that the ionic conductance underlying the HAP persisted briefly after each spike. The HAP had a reversal potential of -85 mV and was unaffected by intracellular Cl- ionophoresis of during exposure to elevated extracellular concentrations of Mg2+. In contrast, the peak amplitude of the HAP was proportional to the extracellular Ca2+ concentration and could be reversibly eliminated by replacing Ca2+ with Co2+, Mn2+, or EGTA in the perfusion fluid. During depolarizing current pulses, evoked action potential trains demonstrated a progressive increase in interspike intervals associated with a potentiation of successive HAPs. This spike frequency adaptation was reversibly abolished by replacing Ca2+ with Co2+, Mn2+, or EGTA. Bursts of action potentials were followed by a more prolonged afterhyperpolarization (AHP) whose magnitude was proportional to the number of impulses elicited (greater than 20 Hz) during a burst. Current injection revealed that the AHP was associated with a 20-60% decrease in input resistance and showed little voltage dependence in the range of -70 to -120 mV. The reversal potential of the AHP shifted with the extracellular concentration of K+ [( K+]o) with a mean slope of -50 mV/log[K+]o.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrical Properties and Anion Permeability of Doubly Rectifying Junctions in the Leech Central Nervous System

1988 ◽  
Vol 137 (1) ◽  
pp. 1-11
Author(s):  
Susan E. Acklin
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Action Potentials ◽  
Sodium Pump ◽  
Current Flow ◽  
Cell Movement ◽  
Voltage Dependent ◽  
Electrical Connections

A study has been made of the electrical connections between touch sensory (T) neurones in the leech central nervous system (CNS) which display remarkable double rectification: depolarization spreads in both directions although hyperpolarization spreads poorly. Tests were made to determine whether this double rectification was a property of the junctions themselves or whether it resulted from changes in the length constants of processes intervening between the cell body and the junctions. Following trains of action potentials, T cells and their fine processes within the neuropile became hyperpolarized through the activity of an electrogenie sodium pump. When any T cell was hyperpolarized by 25 mV by repetitive stimulation, hyperpolarization failed to spread to the T cells to which it was electrically coupled. Further evidence for double rectification of junctions linking T cells was provided by experiments in which Cl− was injected electrophoretically. Cl− injection into one T cell caused inhibitory potentials recorded in it to become reversed. After a delay, Cl− spread to reverse IPSPs in the coupled T cell. Movement of Cl−, like current flow, was dependent on membrane potential. When the T cell into which Cl− was injected was kept hyperpolarized, Cl− failed to move into the adjacent T cell. Upon release of the hyperpolarization in the injected T cell, Cl− moved and reversed IPSPs in the coupled T cell. Together these results indicate that the gating properties of channels linking T cells are voltage-dependent, such that depolarization of either cell allows channels to open whereas hyperpolarization causes them to close.

Electrical properties and innervation of fibers in the orbital layer of rat extraocular muscles

1989 ◽  
Vol 61 (1) ◽  
pp. 116-125 ◽  
Author(s):  
J. Jacoby ◽  
D. J. Chiarandini ◽  
E. Stefani
Keyword(s):  
Electrical Properties ◽  
Nerve Stimulation ◽  
Action Potentials ◽  
Time Course ◽  
Lucifer Yellow ◽  
Extraocular Muscles ◽  
Resting Potential ◽  
Inferior Rectus ◽  
End Plate ◽  
Orbital Layer

1. The inferior rectus muscle of rat, one of the extraocular muscles, contains two populations of multiply innervated fibers (MIFs): orbital MIFs, located in the orbital layer of the muscle and global MIFs, found in the global layer. The electrical properties and the responses to nerve stimulation of orbital MIFs were studied with single intracellular electrodes and compared with those of twitch fibers of the orbital layer, MIFs of the global layer, and tonic fibers of the frog. 2. About 90% of the orbital MIFs did not produce overshooting action potentials. In these fibers the characteristics and time course of the responses to nerve stimulation varied along the length of the fibers. Within 2 mm of the end-plate band of the muscle, the responses consisted of several small end-plate potentials (EPPs) and a nonovershooting spike. Distal to 2 mm, the responses in most fibers consisted of large and small EPPs with no spiking response. Some fibers produced very small spikes surmounted on large EPPs. 3. Overshooting action potentials were observed in approximately 10% of the orbital MIFs recorded between the end-plate band and 2 mm distal. The presence or absence of action potentials was not related to the magnitude of the resting potential of the fibers. 4. The threshold of nerve stimulated responses in orbital MIFs was the same as that in orbital twitch fibers. A large number of orbital MIFs had latencies equal to those for the orbital twitch fibers recorded at the same distance from the end-plate band, but the average latency was greater in the MIFs. The latency of orbital MIFs was about one-half of that for the MIFs of the global layer. The values for the effective resistance and membrane time constant of orbital MIFs fell between those for orbital twitch fibers on the one hand, and global MIFs and frog tonic fibers on the other. 5. In order to compare electrical properties with innervation patterns, fibers identified electrophysiologically as orbital MIFs were injected with the fluorescent dye Lucifer yellow and then traced in Epon-embedded, serial transverse sections. In addition to numerous superficial endings distributed along the fibers, a single "en plaque" ending was also found in the end-plate band that resembled the end plates of the adjacent orbital twitch fibers. 6. From these results we conclude that the electrical activity of orbital MIFs varies along the length of the fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-acetylcholine recepotr antibodies.

1976 ◽  
Vol 144 (3) ◽  
pp. 739-753 ◽  
Author(s):  
J M Lindstrom ◽  
A G Engel ◽  
M E Seybold ◽  
V A Lennon ◽  
E H Lambert
Keyword(s):  
Myasthenia Gravis ◽  
Nerve Stimulation ◽  
Neuromuscular Transmission ◽  
Postsynaptic Membrane ◽  
Passive Transfer ◽  
Autoimmune Response ◽  
End Plate ◽  
Experimental Autoimmune Myasthenia Gravis ◽  
Autoimmune Myasthenia ◽  
Experimental Autoimmune

Passive transfer of experimental autoimmune myasthenia gravis (EAMG) was achieved using the gamma globulin fraction and purified IgG from sera of rats immunized with Electrophus electricus (eel) acetylcholine receptor (AChR). This demonstrates the critical role of anti-AChR antibodies in impairing neuromuscular transmission in EAMG. Passive transfer of anti-AChR antibodies from rats with chronic EAMG induced signs of the acute phase of EAMG in normal recipient rats, including invasion of the motor end-plate region by mononuclear inflammatory cells. Clinical, eletrophysiological, histological, and biochemical signs of acute EAMG were observed by 24 h after antibody transfer. Recipient rats developed profound weakness and fatigability, and the posture characteristic of EAMG. Striking weight loss was attributable to dehydration. Recipient rats showed large decreases in amplitude of muscle responses to motor nerve stimulation, and repetitive nerve stimulation induced characteristic decrementing responses. End-plate potentials were not detectable in many muscle fibers, and the amplitudes of miniature end-plate potentials were reduced in the others. Passively transferred EAMG more severely affected the forearm muscles than diaphragm muscles, though neuromuscular transmission was impaired and curare sensitivity was increased in both muscles. Some AChR extracted from the muscles of rats with passively transferred EAMG was found to be complexed with antibody, and the total yield of AChR per rat was decreased. The quantitative decrease in AChR approximately paralleled in time the course of clinical and electrophysiological signs. The amount of AChR increased to normal levels and beyond at the time neuromuscular transmission was improving. The excess of AChR extractable from muscle as the serum antibody level decreased probably represented extrajunctional receptors formed in response to functional denervation caused by phagocytosis of the postsynaptic membrane by macrophages. The amount of antibody required to passively transfer EAMG was less than required to bind all AChR molecules in a rat's musculature. The effectiveness of samll amounts of antibody was probably amplified by the activation of complement and by the destruction of large areas of postsynaptic membrane by phagocytic cells. A self-sustaining autoimmune response to AChR was not provoked in animals with passively transferred EAMG.

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