An electrophysiological investigation of neuro‐muscular transmission in myasthenia gravis

Elmqvist, D.; Hofmann, William W.; Kugelberg, J.; Quastel, D. M. J.

doi:10.1113/jphysiol.1964.sp007495

Cited by 321 publications

(109 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Readily releasable pool (RRP) is a small fraction (2-4%) of all intraterminal vesicles, which are docked (and primed) to the presynaptic active zones and immediately available for release in response to stimulation (Becherer and Rettig, 2006). The second, mobilization pool contains ϳ10 -20% of all vesicles (Elmqvist et al, 1964). Moderate physiological frequencies of stimulation cause continuous redistribution of vesicles between these two pools.…”

Section: Discussionmentioning

confidence: 99%

The Role of cGMP-Dependent Signaling Pathway in Synaptic Vesicle Cycle at the Frog Motor Nerve Terminals

Petrov

Giniatullin²,

Ситдикова³

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

The role of cGMP-dependent pathways in synaptic vesicle recycling in motor nerve endings during prolonged high-frequency stimulation was studied at frog neuromuscular junctions using electrophysiological and fluorescent methods. An increase of intracellular cGMP concentration (8-Br-cGMP or 8-pCPT-cGMP) significantly reduced the cycle time for synaptic vesicles through the enhancement of vesicular traffic rate from the recycling pool to the readily releasable pool and acceleration of fast endocytosis. Pharmacological inhibition of soluble guanylate cyclase or protein kinase G slowed down the rate of recycling as well as endocytosis of synaptic vesicles. The results suggest that cGMP-PKG-dependent pathway serves a significant function in the control of vesicular cycle in frog motor terminals.

show abstract

Section: Discussionmentioning

confidence: 99%

The Role of cGMP-Dependent Signaling Pathway in Synaptic Vesicle Cycle at the Frog Motor Nerve Terminals

Petrov

Giniatullin²,

Ситдикова³

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…[4,5] The history of myasthenia research is fascinating [6] but cannot be reviewed here. The essential findings in the 1960s and 1970s were that the MEPP amplitudes are substantially reduced in muscle biopsies from MG patients [7] and that this is due to loss of the postsynaptic AChRs. [8] The latter finding depended on the discovery of bungarotoin, a snake toxin that binds specifically to the AChRs.…”

Section: Clinical Featuresmentioning

confidence: 99%

Autoimmune disorders of the neuromuscular junction

Lang

Vincent

2009

Current Opinion in Pharmacology

View full text Add to dashboard Cite

The neuromuscular junction (NMJ) is a prototypic synapse although its structure is rather different from those of the central nervous system (CNS). The unmyelinated motor nerve terminals are separated from the postsynaptic membrane by a cleft that contains a basal lamina. This includes many proteins such as collagens, laminins, fibronectin and perlecan which help anchor some of the key elements involved in NMJ The neuromuscular junction (NMJ) is a specialized synapse with a complex structural and functional organization. It is a target for a variety of immunological disorders and these diseases usually respond well to immunotherapies. The understanding of the immunological basis of myasthenia gravis, the most common neuromuscular junction disorder, has improved in the recent years. Most patients have antibodies to the acetylcholine receptor (AChR), but around 10% have AChR antibodies that are only identified by novel methods, and up to 5% have muscle-speciÞ c kinase antibodies which deÞ ne a different subgroup of myasthenia. The spectrum of antibodies and their pathophysiological aspects are being elucidated. Even though less common, Lambert Eaton myasthenic syndrome (LEMS) is important to recognize. The abnormality in LEMS is a presynaptic failure to release enough packets of ACh, caused by antibodies to the presynaptic voltage-gated calcium channels. More than half these patients have a small cell carcinoma of lung. Acquired neuromyotonia (NMT) is a condition associated with muscle hyperactivity. Clinical features include muscle stiffness, cramps, myokymia, pseudomyotonia and weakness. The immune mechanisms of acquired NMT relate to loss of voltage-gated potassium channel function. This review will focus on the important recent developments in the immunemediated disorders of the NMJ.Key words: Gravis, Lambert Eaton myasthenic syndrome, neuromyotonia, neuromuscular junction, autoimmunity, acetylcholine receptor, voltage-gated channel development and function; for instance acetylcholine esterase (AChE) is localized via ColQ, a collagen-like molecule, to the basal lamina. Agrin and neuregulins, secreted from the nerve terminal, are bound by the basal lamina and interact with their receptors, playing an important role in the location of postsynaptic membrane proteins, voltage-gated calcium channels and the dystroglycans. The postsynaptic membrane at the NMJ forms a series of deep folds. The acetylcholine receptors (AChRs) are found at the top one-third of these folds, whereas the voltage-gated sodium channels are anchored at the bottom of the folds. The development of the NMJ is a fascinating area of research [1] and many of the proteins involved are relevant to disease ([ Figure 1] for a simple representation).The nerve action potential opens voltage-gated calcium channels (VGCCs) that are located in the motor nerve terminal [ Figure 1]. The resulting influx of calcium leads to the release of about 30 (in human muscle) individual packets of acetylcholine (ACh). Some of the ACh is hydrolysed by AChE but about 65%...

show abstract

“…Earlier studies have demonstrated that at human end-plates affected by the disease myasthenia gravis (MG) the spontaneous miniature end-plate potentials (m.e.p.p.s) and impulse evoked end-plate potentials (e.p.p.s) are unusually small (Elmqvist, Hofmann, Kugelberg & Quastel, 1964;Albuquerque, Rash, Mayer & Satterfield, 1976;Ito, Miledi, Molenaar, Vincent, Polak, van Gelder & Newsom Davis, 1976). In addition the over-all binding of labelled a-bungarotoxin (a-BuTx) at the MG end-plate is diminished, in some cases, down to 10% of the normal (Fambrough, Drachman & Satyamurti, 1973;Green, Miledi, Perez de la Mora & Vincent, 1975;Ito, Miledi, Vincent & Newsom Davis, 1978) and the post-synaptic sensitivity to ionophoretically applied ACh is markedly reduced (Albuquerque et al 1976).…”

Section: Introductionmentioning

confidence: 99%

End‐plate currents and acetylcholine noise at normal and myasthenic human end‐plates.

Cull-Candy¹,

Miledi²,

Trautmann³

1979

The Journal of Physiology

View full text Add to dashboard Cite

5. In response to steady ionophoretically applied ACh the mean membrane currents obtained at MG end-plates were smaller than the normal under similar conditions. 6. Analysis of end-plate current noise obtained during the steady application of acetylcholine (ACh) to voltage clamped normal and MG human end-plates showed that the amplitude of the elementary current event (y) and the average channel life-time (Tnoise) was similar at the two sites: Tnoise (normal) = 1t54 + 0-04 msec, Tnoise (MG)= 1-63 + 011 msec; y(normal) = 22-3 + 157 pS, y (MG) = 20-25 + 1-93 pS (Vm = -80 mV, T = 23 TC). The voltage sensitivity of the channel life time, measured from end-plate current noise, was similar at normal and MG endplates.7. At normal human end-plates a packet of transmitter opens about 1500 channels whereas at MG end-plates a packet opens only about 600 channels. It is calculated that the size of the transmitter packets released from MG-terminals is at least as large as the packet of the ACh released from normal human nerve terminals.

show abstract

An electrophysiological investigation of neuro‐muscular transmission in myasthenia gravis

Cited by 321 publications

References 21 publications

The Role of cGMP-Dependent Signaling Pathway in Synaptic Vesicle Cycle at the Frog Motor Nerve Terminals

The Role of cGMP-Dependent Signaling Pathway in Synaptic Vesicle Cycle at the Frog Motor Nerve Terminals

Autoimmune disorders of the neuromuscular junction

End‐plate currents and acetylcholine noise at normal and myasthenic human end‐plates.

Contact Info

Product

Resources

About