Equilibrium potentials of postsynaptic membrane activated by various cholinomimetics during changes in extracellular ionic medium

1969 ◽  
Vol 3 (3) ◽  
pp. 41-50
Author(s):  
V. L. Dunin-Barkovskii ◽  
S. A. Kovalev ◽  
L. G. Magazanik ◽  
T. V. Potapova ◽  
L. M. Chailakhyan
Keyword(s):  
Postsynaptic Membrane ◽  
Ionic Medium

scholarly journals Processing of ARIA and release from isolated nerve terminals

1999 ◽  
Vol 354 (1381) ◽  
pp. 411-416 ◽  
Author(s):  
Bomie Han ◽  
Gerald D. Fischbach
Keyword(s):  
Neuromuscular Junction ◽  
Action Potential ◽  
Acetylcholine Receptors ◽  
Molecular Layer ◽  
Postsynaptic Membrane ◽  
High Density ◽  
Small Contribution ◽  
Presynaptic Nerve Terminal ◽  
Voltage Gated

The neuromuscular junction is a specialized synapse in that every action potential in the presynaptic nerve terminal results in an action potential in the postsynaptic membrane, unlike most interneuronal synapses where a single presynaptic input makes only a small contribution to the population postsynaptic response. The postsynaptic membrane at the neuromuscular junction contains a high density of neurotransmitter (acetylcholine) receptors and a high density of voltage–gated Na + channels. Thus, the large acetylcholine activated current occurs at the same site where the threshold for action potential generation is low. Acetylcholine receptor inducing activity (ARIA), a 42 kD protein, that stimulates synthesis of acetylcholine receptors and voltage–gated Na + channels in cultured myotubes, probably plays the same roles at developing and mature motor endplates in vivo . ARIA is synthesized as part of a larger, transmembrane, precursor protein called proARIA. Delivery of ARIA from motor neuron cell bodies in the spinal cord to the target endplates involves several steps, including proteolytic cleavage of proARIA. ARIA is also expressed in the central nervous system and it is abundant in the molecular layer of the cerebellum. In this paper we describe our first experiments on the processing and release of ARIA from subcellular fractions containing synaptosomes from the chick cerebellum as a model system.

Synaptic transmission and its duplication by focally applied acetylcholine in parasympathetic neurons in the heart of the frog

1971 ◽  
Vol 177 (1049) ◽  
pp. 509-539 ◽  
Keyword(s):  
Synaptic Transmission ◽  
Ganglion Cells ◽  
Postsynaptic Membrane ◽  
Equilibrium Potential ◽  
Neuronal Membrane ◽  
Excitatory Postsynaptic Potential ◽  
Parasympathetic Nerve ◽  
Iontophoretic Application ◽  
Synaptic Boutons ◽  
Synaptic Transmitter

Synaptic transmission has been analysed in parasympathetic nerve cells that lie in the transparent interatrial septum of the heart of the frog. Using Nomarski interference optics, one can see much cellular detail, including synaptic boutons in living preparations. 1. On each ganglion cell, the 10 to 20 synaptic boutons are usually derived from a single vagal nerve fibre. These fibres branch extensively to innervate a number of septal ganglion cells. 2. The chemical transmitter, acetylcholine (ACh), liberated by a presynaptic impulse survives for up to 40 ms, setting up an excitatory postsynaptic potential (e.p.s.p.) which triggers one and sometimes two action potentials in the postsynaptic cell. The e.p.s.p. is made up of quantal components, as at the neuromuscular junction. 3. Nerve-evoked e.p.s.p.s can be well matched in amplitude and time course by iontophoretic application of ACh to selected areas of the neuronal membrane. In particular, the miniature e.p.s.p., which is due to the focal release of a small quantity of transmitter, was accurately mimicked by iontophoretic application of ACh. By grading the amount of ACh released from an electrode one could also duplicate the wide variety of nerve-evoked postsynaptic discharges of ganglion cells. 4. The permeability changes initiated in the postsynaptic membrane by applied ACh and the synaptic transmitter appear identical, since the ionic fluxes for both responses have the same equilibrium potential. Also, the receptors which react with the synaptic transmitter are desensitized by applied ACh. 5. Cholinesterase inhibitors (Tensilon and Eserine) have a variable action on different cells, with respect both to nerve-evoked and Ach evoked potentials. The reasons for this variation are unclear, and need further study. 6. Miniature e.p.s.p.s resemble analogous potentials at nerve-muscle junctions and other synapses. A significant proportion of the min e.p.s.p.s is released as multiple units. This proportion is increased in high Ca2+, while single units alone occur in a low Ca2+-high Mg2+ environment. 7. The experiments provide information about the release of ACh from nerve terminals and its action on the postsynaptic membrane of neurons. They are in good agreement with analogous studies on skeletal neuromuscular junctions

scholarly journals Fc-Receptor Targeted Therapies for the Treatment of Myasthenia gravis

2021 ◽  
Vol 22 (11) ◽  
pp. 5755
Author(s):  
Christian W. Keller ◽  
Marc Pawlitzki ◽  
Heinz Wiendl ◽  
Jan D. Lünemann
Keyword(s):  
Myasthenia Gravis ◽  
Acetylcholine Receptors ◽  
Postsynaptic Membrane ◽  
Fc Receptor ◽  
Igg Antibodies ◽  
Effector Functions ◽  
Disease Remission ◽  
Disease Mechanisms ◽  
First Choice ◽  
Complement Deposition

Myasthenia gravis (MG) is an autoimmune disease in which immunoglobulin G (IgG) antibodies (Abs) bind to acetylcholine receptors (AChR) or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction. IgG crystallizable fragment (Fc)-mediated effector functions, such as antibody-dependent complement deposition, contribute to disease development and progression. Despite progress in understanding Ab-mediated disease mechanisms, immunotherapy of MG remained rather unspecific with corticosteroids and maintenance with immunosuppressants as first choice drugs for most patients. More specific therapeutic IgG Fc-based platforms that reduce serum half-life or effector functions of pathogenic MG-related Abs are currently being developed, tested in clinical trials or have recently been successfully translated into the clinic. In this review, we illustrate mechanisms of action and clinical efficacies of emerging Fc-mediated therapeutics such as neonatal Fc receptor (FcRn)-targeting agents. Furthermore, we evaluate prospects of therapies targeting classical Fc receptors that have shown promising therapeutic efficacy in other antibody-mediated conditions. Increased availability of Fc- and Fc receptor-targeting biologics might foster the development of personalized immunotherapies with the potential to induce sustained disease remission in patients with MG.

Na current density at and away from end plates on rat fast- and slow-twitch skeletal muscle fibers

1992 ◽  
Vol 262 (1) ◽  
pp. C229-C234 ◽  
Author(s):  
R. L. Ruff
Keyword(s):  
Skeletal Muscle ◽  
Current Density ◽  
Muscle Fibers ◽  
Postsynaptic Membrane ◽  
Na Current ◽  
End Plate ◽  
Skeletal Muscle Fibers ◽  
Slow Twitch ◽  
Slow Twitch Fibers ◽  
Fast Twitch

Na current density and membrane capacitance were studied with the loose patch voltage clamp technique on rat fast- and slow-twitch skeletal muscle fibers at three different regions on the fibers: 1) the end plate border, 2) greater than 200 microns from the end plate (extrajunctional), and 3) on the end plate postsynaptic membrane. Fibers were treated with collagenase to improve visualization of the end plate and to enzymatically remove the nerve terminal. The capacitance of membrane patches was similar on fast- and slow-twitch fibers and patches of membrane on the end plate had twice the capacitance of patches elsewhere. For fast- and slow-twitch fibers, the sizes of the Na current normalized to the area of the patch were as follows: end plate greater than end plate border greater than extrajunctional. For both types of fibers, the amplitudes of the Na current normalized to the capacitance of the membrane patch were as follows: end plate approximately end plate border greater than extrajunctional. At each of the three regions, the Na current densities were larger on fast-twitch fibers and fast-twitch fibers had a larger increase in Na current density at the end plate border compared with extrajunctional membrane.

Structure and innervation of the swim bladder musculature in the weakfish, Cynoscion regalis (Teleostei: Sciaenidae)

1982 ◽  
Vol 60 (8) ◽  
pp. 1955-1967 ◽  
Author(s):  
R. Dana Ono ◽  
Stuart G. Poss
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Muscle Fiber ◽  
Muscle Fibers ◽  
Postsynaptic Membrane ◽  
Motor Endplate ◽  
Central Core ◽  
Swim Bladder ◽  
Motor Endplates ◽  
Cynoscion Regalis

The striated swim bladder muscles of the weakfish Cynoscion regalis are deep red in color but cannot be classified histologically as having typical red fibers. The muscle fibers are homogeneous and average 29.6 ± 5.3 μm in diameter, one-fifth the diameter of the adjacent hypaxialis fibers. Each muscle fiber contains thin, ribbonlike myofibrils which are radially arranged around a central core of mitochondria, glycogen, and sarcoplasmic reticulum. Myofibrils are extremely regular in pattern. Triads occur at the Z line. Numerous mitochondria and muscle nuclei are located at the periphery of each muscle fiber. The muscle fibers are multiply innervated with motor endplates distributed along their entire lengths. Well-developed folding of the postsynaptic membrane, not previously reported in fishes, is present at the motor endplate.

Characterization of postsynaptic Ca2+ signals at the Drosophila larval NMJ

2011 ◽  
Vol 106 (2) ◽  
pp. 710-721 ◽  
Author(s):  
Sunil A. Desai ◽  
Gregory A. Lnenicka
Keyword(s):  
Transmitter Release ◽  
Postsynaptic Membrane ◽  
Synaptic Activity ◽  
Synaptic Efficacy ◽  
Single Action ◽  
Synaptic Homeostasis ◽  
Multiple Transcripts ◽  
Quantal Size ◽  
Intracellular Ca ◽  
Larval Neuromuscular Junction

Postsynaptic intracellular Ca2+ concentration ([Ca2+]i) has been proposed to play an important role in both synaptic plasticity and synaptic homeostasis. In particular, postsynaptic Ca2+ signals can alter synaptic efficacy by influencing transmitter release, receptor sensitivity, and protein synthesis. We examined the postsynaptic Ca2+ transients at the Drosophila larval neuromuscular junction (NMJ) by injecting the muscle fibers with Ca2+ indicators rhod-2 and Oregon Green BAPTA-1 (OGB-1) and then monitoring their increased fluorescence during synaptic activity. We observed discrete postsynaptic Ca2+ transients along the NMJ during single action potentials (APs) and quantal Ca2+ transients produced by spontaneous transmitter release. Most of the evoked Ca2+ transients resulted from the release of one or two quanta of transmitter and occurred largely at synaptic boutons. The magnitude of the Ca2+ signals was correlated with synaptic efficacy; the Is terminals, which produce larger excitatory postsynaptic potentials (EPSPs) and have a greater quantal size than Ib terminals, produced a larger Ca2+ signal per terminal length and larger quantal Ca2+ signals than the Ib terminals. During a train of APs, the postsynaptic Ca2+ signal increased but remained localized to the postsynaptic membrane. In addition, we showed that the plasma membrane Ca2+-ATPase (PMCA) played a role in extruding Ca2+ from the postsynaptic region of the muscle. Drosophila melanogaster has a single PMCA gene, predicted to give rise to various isoforms by alternative splicing. Using RT-PCR, we detected the expression of multiple transcripts in muscle and nervous tissues; the physiological significance of the same is yet to be determined.

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