Neuromuscular Junction & Skeletal Muscle

Vocabulary flashcards covering NMJ anatomy, neurotransmission, synaptic proteins, excitation-contraction coupling, sarcomere structure, regulation, and related muscular dystrophy concepts.

Neuromuscular junction (NMJ)

The chemical synapse between a motor neuron and a skeletal muscle fiber; includes presynaptic terminal, synaptic cleft, and postsynaptic motor end plate.

Motor neuron

A neuron that innervates skeletal muscle fibers, transmitting signals that trigger muscle contraction.

Muscle fiber

A single skeletal muscle cell; part of a motor unit; innervated by a motor neuron.

Motor end plate

The highly folded postsynaptic region of a muscle fiber at the NMJ rich in nicotinic ACh receptors.

Acetylcholine (ACh)

The neurotransmitter released at the NMJ; synthesized in the presynaptic terminal and rapidly degraded in the synaptic cleft.

Choline acetyltransferase (ChAT)

Enzyme that synthesizes ACh from choline and acetyl-CoA in the presynaptic terminal.

Nicotinic acetylcholine receptor (nAChR)

Ligand-gated cation channel on the motor end plate that opens in response to ACh, allowing Na+, K+, and some Ca2+ influx.

End plate potential (EPP)

Local depolarization of the motor end plate caused by ACh receptor activation, leading to muscle action potential if threshold is reached.

SNARE proteins

Family of proteins that mediate vesicle fusion; includes V-SNAREs on vesicles (e.g., synaptobrevin) and T-SNAREs on target membranes (syntaxin, SNAP-25); Ca2+ sensor synaptotagmin triggers fusion.

Synaptobrevin

V-SNARE protein on synaptic vesicles essential for vesicle fusion.

Synaptotagmin

Ca2+ sensor that triggers SNARE-mediated vesicle fusion in response to Ca2+ influx.

Syntaxin

T-SNARE protein on the target membrane that participates in vesicle fusion.

SNAP-25

T-SNARE protein that pairs with syntaxin to mediate vesicle fusion.

ACh release

Ca2+-triggered exocytosis of ACh-containing synaptic vesicles into the synaptic cleft.

Acetylcholinesterase (AChE)

Enzyme that rapidly hydrolyzes ACh in the synaptic cleft to terminate signaling.

Myasthenia gravis (MG)

Autoimmune disease with antibodies against nicotinic ACh receptors, reducing receptor number and causing fatigable muscle weakness.

Lambert-Eaton Myasthenic Syndrome (LEMS)

Autoimmune presynaptic disorder; antibodies against voltage-gated Ca2+ channels reduce ACh release; associated with small-cell lung cancer.

DHP receptor

Dihydropyridine receptor; L-type voltage-gated Ca2+ channel in the T-tubule that acts as the voltage sensor for excitation-contraction coupling.

Ryanodine receptor (RYR)

Ca2+ release channel on the sarcoplasmic reticulum that opens in response to DHP signaling, releasing Ca2+ into the cytosol.

Excitation-contraction coupling

Process by which an action potential leads to muscle contraction via Ca2+ release from the SR and activation of the contractile apparatus.

SERCA pump

Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase; pumps Ca2+ back into the SR to promote muscle relaxation.

Cross-bridge cycling

Process of myosin heads attaching to actin, undergoing a power stroke, releasing ADP and Pi, detaching upon ATP binding, and re-cocking.

Sarcomere

The basic contractile unit of a muscle; defined by Z-discs; contains I band (actin), A band (actin + myosin), and H zone (myosin only).

I band

Region containing actin filaments only; spans from Z-disc to the start of the A band.

A band

Region containing overlap of actin and myosin filaments; length remains constant during contraction.

H zone

Central region of the A band where only myosin filaments are present.

Titin

Large elastic protein spanning from the M line to the Z line; contributes to passive elasticity and helps restore resting length after contraction.

Tropomyosin

Regulatory protein that lies along actin and blocks myosin-binding sites when Ca2+ is low; movement allows cross-bridge formation.

Troponin (TnC, TnI, TnT)

Regulatory complex on actin: TnC binds Ca2+, TnI inhibits actin-myosin interaction, TnT binds tropomyosin.

Actin

Thin filament protein; G-actin polymerizes to F-actin; provides myosin-binding sites for cross-bridge cycling.

Myosin

Thick filament motor protein with ATPase activity; heavy and light chains; forms cross-bridges with actin.

Myofilaments

Thick (myosin) and thin (actin) filaments that compose the sarcomere.

Duchenne muscular dystrophy (DMD)

X-linked recessive disease caused by dystrophin deficiency; membrane fragility leads to progressive muscle weakness.

Dystrophin

Cytoskeletal protein linking the muscle cell membrane to the extracellular matrix; its loss destabilizes the membrane in DMD.

Sarcolemma

Plasma membrane of a muscle fiber.

T-tubules

Transverse invaginations of the sarcolemma that propagate action potentials into the interior of the muscle fiber.

Terminal cisternae

Expanded regions of the sarcoplasmic reticulum adjacent to T-tubules; form the triad for Ca2+ release.

Sarcoplasmic reticulum (SR)

Organelle storing Ca2+ in muscle cells; releases Ca2+ via RYR and reuptakes via SERCA.

Z disk

Protein disk defining the borders of a sarcomere; anchors actin filaments.

M line

Midline structure within the sarcomere that anchors myosin filaments.

Epimysium

Connective tissue surrounding the entire muscle.

Perimysium

Connective tissue surrounding a fascicle of muscle fibers.

Endomysium

Connective tissue surrounding each individual muscle fiber.

MG vs. LEMS

Myasthenia Gravis (MG) is an autoimmune disorder that leads to weakness in skeletal muscles due to disrupted communication at the neuromuscular junction, whereas Lambert-Eaton Myasthenic Syndrome (LEMS) is caused by antibodies that disrupt the release of acetylcholine, leading to similar muscle weakness but often with different treatment approaches.

What happens if acetylcholine esterase is inhibited?

Acetylcholine accumulates in the synaptic cleft, leading to prolonged stimulation of the postsynaptic neuron and potential muscle overstimulation, which may result in spasms or paralysis.

Why doesn’t anti-acetylcholine esterase therapy work on somebody with LEMS?

Anti-acetylcholine esterase therapy is ineffective because the underlying problem is at the presynaptic level, specifically with calcium channels, resulting in insufficient acetylcholine release, not a degradation problem. Enhanced neurotransmission with repetitive stimulation actually improves in limbs so encourage them to exercise due to the repeated propagation of action potentials to push the VGCa2+ to try flooding the presynaptic neuron to force out acetylcholine.

LEMS is oftentimes accompanied up to 60% of the time with…

small cell lung cancer