Neuromuscular Junction Quiz

Neuromuscular Junction

• Motor axons communicate with skeletal muscles through neuromuscular junctions (NMJs), also known as end plates.
• Each NMJ forms a synapse between a motor neuron and a muscle fiber.

Motor Unit Composition

• A motor unit consists of a single motor neuron and the muscle fibers it innervates at the NMJ.
• Terminal endings of the motor neuron connect to the motor end plate.

Motor End Plate Structure

• The motor end plate is a specialized region of the muscle fiber's sarcolemma, oval-shaped, covering about 3000 µm².
• Its surface features deep folds with numerous crests and secondary clefts to increase receptor density.

Neuromuscular Junction Events

• Key events include the release of acetylcholine (ACh), binding to receptors, muscle contraction, and subsequent removal of ACh.

Release of Acetylcholine

• Action potentials trigger depolarization in the presynaptic terminal, opening voltage-gated Ca²⁺ channels and increasing intracellular Ca²⁺.
• 100-300 vesicles release ACh into the synaptic cleft through exocytosis.

Binding of Acetylcholine

• ACh molecules diffuse across the synaptic gap to the motor end plate, binding to receptors concentrated on the folds.
• Binding of two ACh molecules to each receptor induces conformational changes.

Muscle Contraction Mechanism

• Conformational changes from ACh binding open ion channels, allowing Na⁺ influx and localized depolarization, known as end plate potentials (EPPs).
• If EPPs exceed a threshold (-50 mV), voltage-gated Na⁺ channels open, propagating a muscle action potential that leads to contraction.

Synthesis and Recycling of Acetylcholine

• ACh is synthesized from choline and acetyl CoA by choline acetyltransferase in motor neuron terminals.
• Recycled ACh comes from extracellular fluid (50%) and the breakdown at NMJs (50%).

Regulation of Choline Acetyltransferase

• Choline acetyltransferase is inhibited by ACh and activated by nerve stimulation.

Storage of Acetylcholine

• Once synthesized, ACh is stored in vesicles within the terminal button, with about 10,000 molecules per vesicle.
• Storage occurs via a magnesium-dependent transport system.

Types of Vesicle Stores

• 1% of vesicles are immediately releasable, 80% are readily releasable, and the remainder is in a stationary store.

Causes of Acetylcholine Release

• ACh may be released spontaneously or in response to a nerve impulse.
• Spontaneous release creates miniature end plate potentials with an unclear function.

Types of ACh Receptors

• There are two main types: nicotinic and muscarinic receptors.
• Nicotinic receptors function in muscle contraction, while muscarinic receptors are involved in various physiological responses.

Nicotinic Acetylcholine Receptors

• Found on the post-junctional side of the motor end plate, with an average of 50 million receptors contributing to signal transmission.
• Comprised of five polypeptide subunits forming a pore for ion flow.

Function of Nicotinic Receptors

• Two ACh molecules must bind to the alpha subunit, leading to ion channel opening, which facilitates the muscle action potential and contraction.

Extra-Junctional Receptors

• Acetylcholine receptors located outside the NMJ are called extra-junctional receptors, mostly in small numbers.
• Highest concentration observed around the motor end plate in the peri-junctional zone.

Muscarinic Acetylcholine Receptor Structure

• These are seven transmembrane G-protein coupled receptors that vary in structure based on tissue type and developmental stage.

Types of Muscarinic Receptors

• Classified into M1, M3, M5 (excitatory) and M2, M4 (inhibitory), influencing various physiological responses.

Muscarinic Receptor Mechanism

• Unlike nicotinic receptors, muscarinic receptors utilize G-proteins which, upon ACh binding, change shape to activate second messengers instead of directly opening ion channels.

Prejunctional Receptors

• Located on the pre-terminal bulb, prejunctional receptors enhance transmitter production when ACh binds, contributing to positive feedback in active NMJs.

Role of Acetylcholinesterase

• ACh must be quickly removed from the synaptic cleft to reset the system, achieved by hydrolysis into choline and acetate via acetylcholinesterase (AchE).

Acetylcholinesterase Structure

• Comprises an ionic site with a glutamate residue and an esteratic site with a serine residue that facilitates hydrolysis.

Hydrolysis Process of Acetylcholine

• Hydrolysis transfers the acetyl group to serine, yielding free choline and acetate.

Inhibition of Acetylcholinesterase

• Inhibitors like malathion, parathion, and eserine prevent ACh hydrolysis, leading to prolonged end plate potentials, impacting muscle function.

Test your knowledge on the neuromuscular junction, including its structure, function, and the events involved in muscle contraction. This quiz will cover key concepts such as motor units, acetylcholine release, and the anatomy of motor end plates.