Give the sequence of events at the neuromuscular junction during the transmission of a nerve impulse. Name the muscles most commonly affected by myasthenia gravis.

Sequence of Events at the Neuromuscular Junction

The transmission of a nerve impulse across the NMJ is a complex process involving several distinct steps:

1. Nerve Impulse Arrival: An action potential, an electrical signal, travels down the motor neuron axon to the axon terminal.
2. Calcium Influx: Depolarization of the axon terminal opens voltage-gated calcium channels, allowing calcium ions (Ca²⁺) to enter the terminal.
3. Acetylcholine Release: The influx of Ca²⁺ triggers the fusion of vesicles containing the neurotransmitter acetylcholine (ACh) with the presynaptic membrane. This process, called exocytosis, releases ACh into the synaptic cleft.
4. ACh Diffusion & Binding: ACh diffuses across the synaptic cleft and binds to nicotinic acetylcholine receptors (nAChRs) located on the motor end plate of the muscle fiber.
5. End Plate Potential (EPP) Generation: The binding of ACh to nAChRs causes the opening of ligand-gated ion channels, allowing Na⁺ ions to flow into the muscle fiber, creating an EPP.
6. Muscle Fiber Depolarization: If the EPP reaches the threshold potential, it triggers an action potential in the muscle fiber.
7. Muscle Contraction: The muscle fiber action potential propagates along the sarcolemma and into the T-tubules, leading to the release of calcium from the sarcoplasmic reticulum and initiating muscle contraction.
8. ACh Degradation: Acetylcholinesterase (AChE), an enzyme present in the synaptic cleft, rapidly breaks down ACh into choline and acetate, terminating the signal. Choline is then taken back up into the presynaptic neuron for reuse.

Myasthenia Gravis: Affected Muscles

Myasthenia gravis is an autoimmune disorder where antibodies attack the nAChRs at the NMJ, reducing the number of available receptors. This impairs the transmission of nerve impulses, leading to muscle weakness. The muscles most commonly affected by myasthenia gravis are those controlling:

• Ocular Muscles: Ptosis (drooping eyelids) and diplopia (double vision) are often the first symptoms, affecting approximately 50% of patients.
• Bulbar Muscles: These muscles control speech, swallowing, and chewing. Weakness in these muscles leads to dysarthria (slurred speech), dysphagia (difficulty swallowing), and difficulty chewing.
• Facial Muscles: Weakness of facial muscles causes a characteristic "masked" facial expression.
• Limb Muscles: Proximal limb muscles (shoulders and hips) are more commonly affected than distal muscles, leading to difficulty raising arms or climbing stairs.
• Respiratory Muscles: In severe cases, myasthenia gravis can affect the respiratory muscles, leading to respiratory failure – a myasthenic crisis.

The pattern of muscle involvement can vary significantly between individuals. The severity of symptoms also fluctuates, often worsening with activity and improving with rest.

Muscle Group	Common Symptoms in Myasthenia Gravis
Ocular	Ptosis, Diplopia
Bulbar	Dysarthria, Dysphagia
Facial	Masked facial expression
Limb	Proximal muscle weakness
Respiratory	Shortness of breath, Respiratory failure