Neuromuscular junction

Quantal transmission [ ] At the neuromuscular junction presynaptic motor axons terminate 30 nanometers from the cell membrane or 2. 2, held in place by the structural proteins About once every second in a resting junction randomly one of the synaptic vesicles fuses with the presynaptic neuron's [ citation needed] When the motor nerve is stimulated there is a delay of only 0.5 to 0.8 msec between the arrival of the nerve impulse in the motor nerve terminals and the first response of the endplate 2+ 2+ causes several hundred 2+ channels which are mechanically coupled to Ca 2+ release channels in the sarcoplasmic reticulum. 2+ then diffuses out of the sarcoplasmic reticulum to the myofibrils so it can stimulate contraction. The endplate potential is thus responsible for setting up an action potential in the muscle fiber which triggers muscle contraction. The transmission from nerve to muscle is so rapid because each quantum of acetylcholine reaches the endplate in millimolar concentrations, high enough to combine with a receptor with a low affinity, which then swiftly releases the bound transmitter. [ citation needed] Acetylcholine receptors [ ] • Ion channel linked receptor • • AChRs at the skeletal neuromuscular junction form heteropentamers composed of two α, one β, one ɛ, and one δ subunits. Development [ ] The development of the neuromuscular junction requires signaling from both the motor neuron's terminal and the muscle cell's central region. During development, muscle...

• Neuromuscular junction (NMJ) disorders result from destruction, malfunction or absence of one or more key proteins involved in neuromuscular transmission, illustrated diagrammatically in fig 1. The most common pathology is antibody mediated damage or down regulation of ion channels or receptors, resulting in myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and acquired neuromyotonia (Isaac’s syndrome). Not surprisingly these three conditions share many common features (table 1). A second important group of disorders are the congenital myasthenic syndromes caused by mutations in NMJ proteins. Detailed discussion of these rare conditions is beyond the scope of this short review but interested readers are referred to a recent review by Engel and Ohno. 1 Figure 1 Diagrammatic representation of neuromuscular transmission. (1) Action potential arriving at nerve terminal triggers opening of voltage gated calcium channels (VGCCs) and entry of calcium. (2) Rise in intracellular calcium triggers release of packets of acetylcholine (ACh). (3) Interaction of ACh with ACh receptors (AChR) depolarises post-synaptic membrane. (4) Voltage gated sodium channels (VGSCs) open, triggering muscle action potential. (5) ACh esterase (AChE) breaks ACh into acetyl and choline, which are taken up by the nerve terminal to be reformed into ACh. (6) Opening of voltage gated potassium channels (VGKCs) repolarises nerve terminal. MYASTHENIA GRAVIS Pathophysiology In anti-AChR antibody...

• Striated muscle contracts when it receives an impulse from a motor neurone via the neuromuscular junction • Neuromuscular junctions work in a very similar way to synapses • They are located between a neurone and a muscle cell • When an impulse travelling along the axon of a motor neurone arrives at the presynaptic membrane, the action potential causes calcium ions to diffuse into the neurone • This stimulates vesicles containing the neurotransmitter acetylcholine (ACh) to fuse with the presynaptic membrane • The ACh that is released diffuses across the neuromuscular junction and binds to receptor proteins on the sarcolemma (surface membrane of the muscle fibre cell) • This stimulates ion channels in the sarcolemma to open, allowing sodium ions to diffuse in • This depolarises the sarcolemma, generating an action potential that passes down the T-tubules towards the centre of the muscle fibre • These action potentials cause voltage-gated calcium ion channel proteins in the membranes of the sarcoplasmic reticulum (which lie very close to the T-tubules) to open • Calcium ions diffuse out of the sarcoplasmic reticulum (SR) and into the sarcoplasm surrounding the myofibrils • Calcium ions bind to troponin molecules, stimulating them to change shape • This causes the troponin and tropomyosin proteins to change position on the thin (actin) filaments • The myosin-binding sites are exposed to the actin molecules • The process of muscle contraction (known as the sliding filament mo...

J.A. Simpson MD, FRCP, FRCP (Ed), FRCP (Glas), FRS (Ed), W. Fitch PhD, MB ChB, FFARCS, in Applied Neurophysiology, 1988 Publisher Summary This chapter provides an overview of the neuromuscular junction. The neurotransmitter acetylcholine is synthesized from choline and acetyl coenzyme A and stored in the distal part of motor nerves. Coenzyme A is acetylated with energy that is usually supplied by glucose and adenosine triphosphate. The enzyme acetyltransferase transfers the acetyl groups to choline to form acetylcholine (ACh) that is then stored until required. The coupling between the nerve terminal action potential and the release of transmitter is uncertain. Some of the ACh liberated into the synaptic cleft escapes at the boundaries, but the structure of the mammalian neuromuscular junction is particularly favorable to limit this. Some of the ACh is hydrolyzed by acetylcholinesterase within the cleft and is taken up for resynthesis by the nerve terminal. Most of the free ACh binds with receptors in the subsynaptic membrane of the endplate. Z. Feng, C.-P. Ko, in Encyclopedia of Neuroscience, 2009 Remodeling Mature NMJs are not static, but undergo synaptic remodeling throughout adult life. For example, extension and retraction of nerve terminals can be seen with repeated in vivo observations at frog NMJs in normal intact muscles. Similar to nerve terminals, PSCs are also very dynamic in frog muscles. Using PNA as a vital probe for PSC-associated extracellular matrix, it h...

synapse, also called neuronal junction, the site of transmission of electric At a chemical synapse each ending, or terminal, of a Once they have been released and have bound to postsynaptic receptors, neurotransmitter molecules are immediately deactivated by enzymes in the synaptic cleft; they are also taken up by receptors in the presynaptic membrane and recycled. This process causes a series of brief transmission events, each one taking place in only 0.5 to 4.0 milliseconds. A single neurotransmitter may elicit different responses from different receptors. For example,

synapse, also called neuronal junction, the site of transmission of electric At a chemical synapse each ending, or terminal, of a Once they have been released and have bound to postsynaptic receptors, neurotransmitter molecules are immediately deactivated by enzymes in the synaptic cleft; they are also taken up by receptors in the presynaptic membrane and recycled. This process causes a series of brief transmission events, each one taking place in only 0.5 to 4.0 milliseconds. A single neurotransmitter may elicit different responses from different receptors. For example,

• Striated muscle contracts when it receives an impulse from a motor neurone via the neuromuscular junction • Neuromuscular junctions work in a very similar way to synapses • They are located between a neurone and a muscle cell • When an impulse travelling along the axon of a motor neurone arrives at the presynaptic membrane, the action potential causes calcium ions to diffuse into the neurone • This stimulates vesicles containing the neurotransmitter acetylcholine (ACh) to fuse with the presynaptic membrane • The ACh that is released diffuses across the neuromuscular junction and binds to receptor proteins on the sarcolemma (surface membrane of the muscle fibre cell) • This stimulates ion channels in the sarcolemma to open, allowing sodium ions to diffuse in • This depolarises the sarcolemma, generating an action potential that passes down the T-tubules towards the centre of the muscle fibre • These action potentials cause voltage-gated calcium ion channel proteins in the membranes of the sarcoplasmic reticulum (which lie very close to the T-tubules) to open • Calcium ions diffuse out of the sarcoplasmic reticulum (SR) and into the sarcoplasm surrounding the myofibrils • Calcium ions bind to troponin molecules, stimulating them to change shape • This causes the troponin and tropomyosin proteins to change position on the thin (actin) filaments • The myosin-binding sites are exposed to the actin molecules • The process of muscle contraction (known as the sliding filament mo...

J.A. Simpson MD, FRCP, FRCP (Ed), FRCP (Glas), FRS (Ed), W. Fitch PhD, MB ChB, FFARCS, in Applied Neurophysiology, 1988 Publisher Summary This chapter provides an overview of the neuromuscular junction. The neurotransmitter acetylcholine is synthesized from choline and acetyl coenzyme A and stored in the distal part of motor nerves. Coenzyme A is acetylated with energy that is usually supplied by glucose and adenosine triphosphate. The enzyme acetyltransferase transfers the acetyl groups to choline to form acetylcholine (ACh) that is then stored until required. The coupling between the nerve terminal action potential and the release of transmitter is uncertain. Some of the ACh liberated into the synaptic cleft escapes at the boundaries, but the structure of the mammalian neuromuscular junction is particularly favorable to limit this. Some of the ACh is hydrolyzed by acetylcholinesterase within the cleft and is taken up for resynthesis by the nerve terminal. Most of the free ACh binds with receptors in the subsynaptic membrane of the endplate. Z. Feng, C.-P. Ko, in Encyclopedia of Neuroscience, 2009 Remodeling Mature NMJs are not static, but undergo synaptic remodeling throughout adult life. For example, extension and retraction of nerve terminals can be seen with repeated in vivo observations at frog NMJs in normal intact muscles. Similar to nerve terminals, PSCs are also very dynamic in frog muscles. Using PNA as a vital probe for PSC-associated extracellular matrix, it h...

Quantal transmission [ ] At the neuromuscular junction presynaptic motor axons terminate 30 nanometers from the cell membrane or 2. 2, held in place by the structural proteins About once every second in a resting junction randomly one of the synaptic vesicles fuses with the presynaptic neuron's [ citation needed] When the motor nerve is stimulated there is a delay of only 0.5 to 0.8 msec between the arrival of the nerve impulse in the motor nerve terminals and the first response of the endplate 2+ 2+ causes several hundred 2+ channels which are mechanically coupled to Ca 2+ release channels in the sarcoplasmic reticulum. 2+ then diffuses out of the sarcoplasmic reticulum to the myofibrils so it can stimulate contraction. The endplate potential is thus responsible for setting up an action potential in the muscle fiber which triggers muscle contraction. The transmission from nerve to muscle is so rapid because each quantum of acetylcholine reaches the endplate in millimolar concentrations, high enough to combine with a receptor with a low affinity, which then swiftly releases the bound transmitter. [ citation needed] Acetylcholine receptors [ ] • Ion channel linked receptor • • AChRs at the skeletal neuromuscular junction form heteropentamers composed of two α, one β, one ɛ, and one δ subunits. Development [ ] The development of the neuromuscular junction requires signaling from both the motor neuron's terminal and the muscle cell's central region. During development, muscle...

• Neuromuscular junction (NMJ) disorders result from destruction, malfunction or absence of one or more key proteins involved in neuromuscular transmission, illustrated diagrammatically in fig 1. The most common pathology is antibody mediated damage or down regulation of ion channels or receptors, resulting in myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and acquired neuromyotonia (Isaac’s syndrome). Not surprisingly these three conditions share many common features (table 1). A second important group of disorders are the congenital myasthenic syndromes caused by mutations in NMJ proteins. Detailed discussion of these rare conditions is beyond the scope of this short review but interested readers are referred to a recent review by Engel and Ohno. 1 Figure 1 Diagrammatic representation of neuromuscular transmission. (1) Action potential arriving at nerve terminal triggers opening of voltage gated calcium channels (VGCCs) and entry of calcium. (2) Rise in intracellular calcium triggers release of packets of acetylcholine (ACh). (3) Interaction of ACh with ACh receptors (AChR) depolarises post-synaptic membrane. (4) Voltage gated sodium channels (VGSCs) open, triggering muscle action potential. (5) ACh esterase (AChE) breaks ACh into acetyl and choline, which are taken up by the nerve terminal to be reformed into ACh. (6) Opening of voltage gated potassium channels (VGKCs) repolarises nerve terminal. MYASTHENIA GRAVIS Pathophysiology In anti-AChR antibody...