The effect of Lambert-Eaton myasthenic syndrome antibody on slow action potentials in mouse cardiac ventricle

1988 ◽  
Vol 235 (1278) ◽  
pp. 103-110 ◽  
Keyword(s):  
Action Potentials ◽  
Motor Nerve ◽  
Motor Nerve Terminal ◽  
Nerve Terminals ◽  
Intracellular Recordings ◽  
High K ◽  
Cardiac Ventricle ◽  
Myasthenic Syndrome ◽  
Channel Currents ◽  
Slow Action Potentials

Immunoglobulin G (IgG) from Lambert-Eaton myasthenic syndrome (LEMS) patients acts at motor nerve terminal Ca 2+ channels. It was injected into mice to investigate effects on cardiac Ca 2+ channels. Intracellular recordings were made of slow action potentials in right ventricular muscle cells in the presence of high K + concentrations and isoprenaline (1µM). Reduction in Ca 2+ concentration reduced the rate of rise and amplitude, but not the duration, of slow action potentials whereas verapamil (1µM) blocked them. They were not blocked by tetrodotoxin (10 µM), and 4-aminopyridine (1mM) prolonged the decay phase without affecting the rate of rise and amplitude. The rate of rise, amplitude and duration of slow action potentials were not affected by LEMS IgG. These results show that LEMS IgG does not act on Ca 2+ channel currents that underlie slow action potentials in mouse ventricles, suggesting antigenic differences between Ca 2+ channels at motor nerve terminals and heart.

Passive Transfer of Lambert-Eaton Myasthenic Syndrome Induces Dihydropyridine Sensitivity of I Ca in Mouse Motor Nerve Terminals

1998 ◽  
Vol 80 (3) ◽  
pp. 1056-1069 ◽  
Author(s):  
You-Fen Xu ◽  
Sandra J. Hewett ◽  
William D. Atchison
Keyword(s):  
Slow Component ◽  
Motor Nerve ◽  
Passive Transfer ◽  
Acute Exposure ◽  
Motor Nerve Terminal ◽  
Nerve Terminals ◽  
Motor Nerve Terminals ◽  
Axon Terminals ◽  
Myasthenic Syndrome ◽  
Rat Forebrain

Xu, You-Fen, Sandra J. Hewett, and William D. Atchison. Passive transfer of Lambert-Eaton Myasthenic Syndrome induces dihydropyridine sensitivity of I Ca in mouse motor nerve terminals. J. Neurophysiol. 80: 1056–1069, 1998. Mice were injected for 30 days with plasma from three patients with Lambert-Eaton Myasthenic Syndrome (LEMS). Recordings were made from the perineurial sheath of motor axon terminals of triangularis sterni muscle preparations. The objective was to characterize pharmacologically the identity of kinetically distinct, defined potential changes associated with motor nerve terminal Ca2+ currents ( I Ca) that were affected by LEMS autoantibodies. I Ca elicited at 0.01 Hz were significantly reduced in amplitude by ∼35% of control in LEMS-treated nerve terminals. During 10-Hz stimulation, I Ca amplitude was unchanged in LEMS-treated motor nerve terminals, but was depressed in control. During 20- or 100-Hz trains, facilitation of I Ca occurred in LEMS-treated nerve terminals whereas in control, no facilitation occurred during the trains at 20 Hz and marked depression occurred at 100 Hz. Saturation for amplitude and duration of I Ca in control terminals occurred at 2 and 4–6 mM extracellular Ca2+, respectively; in LEMS-treated terminals, the extracellular Ca2+ concentration had to increase by two to three times of control to cause saturation. Amplitude of the two components of I Ca observed when the preparation was exposed to 50 μM 3,4-diaminopyridine and 1 mM tetraethylammonium were both reduced by LEMS plasma treatment. The fast component ( I Ca,f) was reduced by 35%, whereas the slow component ( I Ca,s) was reduced by 37%. ω-Agatoxin IVA (ω-Aga-IVA; 0.15 μM) and ω-conotoxin-MVIIC (ω-CTx-MVIIC; 5 μM) completely blocked I Ca in control motor nerve terminals. The same concentrations of toxins were 20–30% less effective in blocking I Ca in LEMS-treated terminals. The residual I Ca remaining after treatment with ω-Aga-IVA or ω-CTx-MVIIC was blocked by 10 μM nifedipine and 10 μM Cd2+. Thus LEMS plasma appears to downregulate ω-Aga-IVA-sensitive (P-type) and/or ω-CTx-MVIIC-sensitive (Q- type) Ca2+ channels in murine motor nerve terminals, whereas dihydropyridine (DHP)-sensitive (L-type) Ca2+ channels are unmasked in these terminals. Acute exposure (90 min) of rat forebrain synaptosomes to LEMS immunoglobulins (Igs; 4 mg/ml) did not alter the binding of [3H]-nitrendipine or [125I]-ω-conotoxin-GVIA (-ω-CgTx GVIA) when compared with synaptosomes incubated with an equivalent concentration of control Igs. Conversely, LEMS Igs significantly decreased the B max for [3H]-verapamil to ∼45% of control. The apparent affinity of verapamil ( K D) for the remaining receptors was not significantly altered. Thus acute exposure of isolated central nerve terminals to LEMS Igs does not increase DHP sensitivity, whereas it reduces the number of binding sites for verapamil but not for nitrendipine or ω-CgTx-GVIA. These results suggest that chronic but not acute exposure to LEMS Igs either upregulates or unmasks DHP-sensitive Ca2+ channels in motor nerve endings.

scholarly journals Acetylcholinesterase from the motor nerve terminal accumulates on the synaptic basal lamina of the myofiber.

1991 ◽  
Vol 115 (3) ◽  
pp. 755-764 ◽  
Author(s):  
L Anglister
Keyword(s):  
Basal Lamina ◽  
Ache Activity ◽  
Neuromuscular Junctions ◽  
Motor Nerve ◽  
Synaptic Cleft ◽  
Motor Nerve Terminal ◽  
Nerve Terminals ◽  
Axon Terminals ◽  
Muscle Nerve ◽  
Almost All

Acetylcholinesterase (AChE) in skeletal muscle is concentrated at neuromuscular junctions, where it is found in the synaptic cleft between muscle and nerve, associated with the synaptic portion of the myofiber basal lamina. This raises the question of whether the synaptic enzyme is produced by muscle, nerve, or both. Studies on denervated and regenerating muscles have shown that myofibers can produce synaptic AChE, and that the motor nerve may play an indirect role, inducing myofibers to produce synaptic AChE. The aim of this study was to determine whether some of the AChE which is known to be made and transported by the motor nerve contributes directly to AChE in the synaptic cleft. Frog muscles were surgically damaged in a way that caused degeneration and permanent removal of all myofibers from their basal lamina sheaths. Concomitantly, AChE activity was irreversibly blocked. Motor axons remained intact, and their terminals persisted at almost all the synaptic sites on the basal lamina in the absence of myofibers. 1 mo after the operation, the innervated sheaths were stained for AChE activity. Despite the absence of myofibers, new AChE appeared in an arborized pattern, characteristic of neuromuscular junctions, and its reaction product was concentrated adjacent to the nerve terminals, obscuring synaptic basal lamina. AChE activity did not appear in the absence of nerve terminals. We concluded therefore, that the newly formed AChE at the synaptic sites had been produced by the persisting axon terminals, indicating that the motor nerve is capable of producing some of the synaptic AChE at neuromuscular junctions. The newly formed AChE remained adherent to basal lamina sheaths after degeneration of the terminals, and was solubilized by collagenase, indicating that the AChE provided by nerve had become incorporated into the basal lamina as at normal neuromuscular junctions.

scholarly journals The Frog Motor Nerve Terminal Has Very Brief Action Potentials and Three Electrical Regions Predicted to Differentially Control Transmitter Release

2020 ◽  
Vol 40 (18) ◽  
pp. 3504-3516 ◽  
Author(s):  
Scott P. Ginebaugh ◽  
Eric D. Cyphers ◽  
Viswanath Lanka ◽  
Gloria Ortiz ◽  
Evan W. Miller ◽  
...  
Keyword(s):  
Nerve Terminal ◽  
Transmitter Release ◽  
Action Potentials ◽  
Motor Nerve ◽  
Motor Nerve Terminal

scholarly journals Motor Nerve Terminals As the Site of Initial Functional Changes After Denervation

1969 ◽  
Vol 53 (1) ◽  
pp. 70-80 ◽  
Author(s):  
Michiko Okamoto ◽  
Walter F. Riker
Keyword(s):  
Motor Nerve ◽  
Repetitive Stimulation ◽  
Motor Nerve Terminal ◽  
Nerve Terminals ◽  
In Situ Experiment ◽  
Muscle System ◽  
Motor Nerve Terminals ◽  
Functional Changes ◽  
Post Tetanic Potentiation ◽  
Nerve Muscle

For the cat soleus nerve-muscle system, motor nerve section 48 hr prior to in situ experiment causes certain characteristic transmission losses. Responses to repetitive stimulation are sharply altered: The capacity to transmit iterative stimulation is severely reduced; post-tetanic potentiation and the post-tetanic repetition of soleus nerve terminals responsible for it are also greatly impaired; a phenomenon of post-tetanic depression was frequently observed. However, function of the extramuscular axons appears normal and single impulse transmission is usually not seriously affected. The loss of reactivity to repetitive stimulation has been traced to soleus motor nerve terminals. In view of these data and the known absence of denervation hypersensitivity at this time, the earliest functional failure may be said to occur in the unmyelinated terminals. This subacutely denervated preparation therefore offers a simple means of evaluating motor nerve terminal responsiveness.

scholarly journals Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. II. Autoradiographic evidence for its uptake into motor nerves by acceptor-mediated endocytosis.

1986 ◽  
Vol 103 (2) ◽  
pp. 535-544 ◽  
Author(s):  
J D Black ◽  
J O Dolly
Keyword(s):  
Nerve Terminal ◽  
Time Course ◽  
Motor Nerve ◽  
Endocytic Pathway ◽  
Metabolic Inhibitors ◽  
Motor Nerve Terminal ◽  
Specific Cell ◽  
Nerve Terminals ◽  
Electron Microscopic Autoradiography ◽  
Silver Grains

Using pharmacological (Simpson, L.L., 1980, J. Pharmacol. Exp. Ther. 212:16-21) and autoradiographic techniques (Black, J.D., and J.O. Dolly, 1986, J. Cell Biol., 103:521-534), it has been shown that botulinum neurotoxin (BoNT) is translocated across the motor nerve terminal membrane to reach a postulated intraterminal target. In the present study, the nature of this uptake process was investigated using electron microscopic autoradiography. It was found that internalization is acceptor-mediated and that binding to specific cell surface acceptors involves the heavier chain of the toxin. In addition, uptake was shown to be energy and temperature-dependent and to be accelerated by nerve stimulation, a treatment which also shortens the time course of the toxin-induced neuroparalysis. These results, together with the observation that silver grains were often associated with endocytic structures within the nerve terminal, suggested that acceptor-mediated endocytosis is responsible for toxin uptake. This proposal is supported further by the fact that lysosomotropic agents, which are known to interfere with the endocytic pathway, retard the onset of BoNT-induced neuroparalysis and also affect the distribution of silver grains at nerve terminals treated with 125I-BoNT. Possible recycling of BoNT acceptors (an important aspect of acceptor-mediated endocytosis of toxins) at motor nerve terminals was indicated by comparing the extent of labeling in the presence and absence of metabolic inhibitors. On the basis of these collective results, it is concluded that BoNT is internalized by acceptor-mediated endocytosis and, hence, the data support the proposal that this toxin inhibits release of acetylcholine by interaction with an intracellular target.

Motor Nerve Terminal Calcium Channels in Lambert-Eaton Myasthenic Syndrome.

1989 ◽  
Vol 560 (1 Calcium Chann) ◽  
pp. 278-290 ◽  
Author(s):  
ANDREW G. ENGEL ◽  
ALEXANDRE NAGEL ◽  
TADAHIRO FUKUOKA ◽  
HIDETOSHI FUKUNAGA ◽  
MITSUHIRO OSAME ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Nerve Terminal ◽  
Motor Nerve ◽  
Motor Nerve Terminal ◽  
Myasthenic Syndrome

Steroid anaesthetics: inhibition of depolarization–secretion coupling at the mouse motor nerve terminal

1980 ◽  
Vol 58 (10) ◽  
pp. 1221-1228 ◽  
Author(s):  
P. Pennefather ◽  
E. Puil ◽  
D. M. J. Quastel
Keyword(s):  
Neuromuscular Junction ◽  
Nerve Terminal ◽  
Motor Nerve ◽  
Motor Nerve Terminal ◽  
Nerve Terminals ◽  
Potassium Depolarization ◽  
End Plate

The coupling between nerve terminal depolarization and quantal secretion of acetylcholine at the mouse neuromuscular junction was estimated by measuring the multiplication of the frequency of miniature end-plate potentials (m.e.p.p.s) produced by increasing the concentration of calcium in the medium from 0.1 to 1.0 mM in the presence of 15 mM potassium. Depolarization–secretion coupling was inhibited by the anaesthetic steroids progesterone, pregnanedione, and alphaxalone. The nonanaesthetic steroid Δ16-alphaxalone also inhibited depolarization–secretion coupling with the same potency as alphaxalone. This result indicates that inhibition of depolarization–secretion coupling in nerve terminals is unlikely to play a major role in the production of anaesthesia.

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