Nerve-Muscle Physiology & CNS

1. What this chapter covers, and how NEET PG actually tests it

Neuromuscular questions describe weakness and ask where in the chain it arose.

That chain has a fixed sequence: an action potential travels down an axon, calcium enters the nerve terminal, transmitter is released, a receptor is activated, the muscle membrane depolarises, calcium is released internally, and cross-bridges cycle.

Each step has its own diseases, and each disease has a signature that identifies the step.

Myasthenia gravis and Lambert-Eaton syndrome are the cleanest illustration. Both cause weakness, but one worsens with activity and the other improves — and that difference is a direct readout of whether the defect is presynaptic or postsynaptic.

This chapter covers membrane and action potentials with nerve fibre types, the neuromuscular junction, excitation-contraction coupling and muscle mechanics, and reflex physiology with sleep.

2. Membrane and action potentials

2.1 What sets the resting potential

The resting membrane potential is roughly −70 mV in a neuron and −90 mV in skeletal muscle.

It sits close to the equilibrium potential for potassium because the resting membrane is far more permeable to potassium than to anything else.

The Nernst equation gives the equilibrium potential for a single ion at body temperature:

$E_{ion}=\frac{61}{z}\log \frac{[ion{]}_{out}}{[ion{]}_{in}}$

For potassium this yields about −90 mV. The measured resting potential is slightly less negative because a small sodium leak pulls it upward.

The sodium-potassium ATPase contributes directly but modestly, exporting three sodium for every two potassium imported.

Its larger contribution is indirect — it maintains the concentration gradients on which every potential in the chain depends.

2.2 The action potential and the two refractory periods

Depolarisation to threshold opens voltage-gated sodium channels, and these have two gates rather than one.

The activation gate opens rapidly on depolarisation; the inactivation gate closes more slowly, terminating the influx.

This two-gate arrangement is the whole explanation of refractoriness.

During the absolute refractory period, sodium channels are inactivated and no stimulus of any strength can trigger another action potential, because the inactivation gate reopens only after repolarisation.

During the relative refractory period, some channels have recovered but potassium conductance remains elevated, so a stronger-than-normal stimulus is required.

The absolute refractory period is what makes conduction unidirectional, since the membrane just behind the impulse cannot be re-excited.

Conduction velocity rises with axon diameter and with myelination, which allows saltatory conduction between nodes of Ranvier.

2.3 Nerve fibre types and selective vulnerability

Fibres are classified by diameter and myelination, and the classification predicts both function and vulnerability.

The vulnerability rules run in opposite directions for the two commonest insults, and this is heavily tested.

Local anaesthetics block small myelinated fibres first, so the clinical sequence of loss is pain and temperature, then touch, then motor function.

Pressure and hypoxia block large fibres first, which is why a compressed limb loses proprioception and motor power while pain sensation persists — the reason a "dead" arm still hurts.

3. The neuromuscular junction

3.1 The sequence of transmission

The action potential arriving at the terminal opens P/Q-type voltage-gated calcium channels.

Calcium entry triggers fusion of acetylcholine-containing vesicles with the membrane, releasing transmitter in discrete quanta.

Acetylcholine crosses the cleft and binds nicotinic receptors on the motor end plate, opening a cation channel and producing an end-plate potential.

The end-plate potential is normally far larger than needed to reach threshold, and this excess is called the safety factor.

That margin explains why a substantial proportion of receptors must be lost before weakness appears clinically.

Acetylcholinesterase in the cleft then terminates the signal by hydrolysing the transmitter.

3.2 Four disorders, four different steps

Each classic neuromuscular disorder attacks a different point in that sequence, and its clinical signature reports which one.

The myasthenia and Lambert-Eaton contrast is worth reasoning through rather than memorising.

In myasthenia the receptors are depleted, so each successive release finds fewer targets and repeated use exhausts the safety factor — weakness worsens with activity.

In Lambert-Eaton the calcium channels are blocked, so little transmitter is released initially. Sustained activity allows calcium to accumulate in the terminal, transmitter release improves, and strength briefly increases.

Tetanus is the one that produces spasticity rather than weakness, because the toxin blocks release of the inhibitory transmitters glycine and GABA rather than acetylcholine. Removing inhibition leaves motor neurons firing unopposed.

Botulinum toxin acts at the opposite end of the same logic, preventing acetylcholine release and causing flaccid paralysis — which is why it is used therapeutically for dystonia and spasticity.

4. Excitation-contraction coupling and muscle mechanics

4.1 How a membrane signal becomes calcium

The end-plate potential triggers an action potential that spreads along the sarcolemma and into the T tubules.

There it activates the dihydropyridine receptor, a voltage sensor in the T tubule membrane.

In skeletal muscle the dihydropyridine receptor is mechanically coupled to the ryanodine receptor on the sarcoplasmic reticulum, so the conformational change directly opens the calcium release channel.

No extracellular calcium is required, which is why skeletal muscle continues to contract in a calcium-free bath for some time.

Cardiac muscle works differently and the distinction is examinable. There the dihydropyridine receptor is itself a calcium channel, and the calcium that enters triggers further release from the sarcoplasmic reticulum — calcium-induced calcium release.

Cardiac contraction therefore genuinely depends on extracellular calcium, which is why calcium channel blockers reduce cardiac contractility but do not weaken skeletal muscle.

4.2 The cross-bridge cycle and rigor mortis

Released calcium binds troponin C, moving tropomyosin off the myosin-binding sites on actin.

The cycle then proceeds in four steps. Myosin binds actin, releases inorganic phosphate and performs the power stroke, and the head remains attached in a rigor state until ATP binds and detaches it. Hydrolysis of that ATP then re-cocks the head.

Note that ATP is required for detachment, not for the power stroke itself.

That single fact explains rigor mortis. When ATP is exhausted after death, myosin heads cannot detach and the muscle remains rigid until proteolysis eventually breaks the bonds.

Relaxation is also active. Calcium must be pumped back into the sarcoplasmic reticulum by the SERCA pump, which consumes ATP.

4.3 Smooth muscle uses a different switch

Smooth muscle has no troponin, so calcium cannot act the same way.

Instead calcium binds calmodulin, which activates myosin light chain kinase, which phosphorylates the myosin light chain and enables cross-bridge cycling.

The regulation is therefore on the myosin side in smooth muscle and on the actin side in striated muscle, which is a clean way to hold the distinction.

Smooth muscle can also maintain tension at low energy cost in the latch state, with slowly cycling attached cross-bridges — the mechanism behind sustained vascular tone.

4.4 Length-tension and force summation

Active tension depends on how much actin and myosin overlap, so it is maximal at an intermediate sarcomere length.

Stretch the muscle too far and the filaments barely overlap; let it shorten too much and the thin filaments collide. Either way force falls.

This is the cellular basis of the Frank-Starling relationship in the heart, and it is why the ventricle has an optimal filling volume rather than an unlimited one.

Skeletal muscle can also grade its force in two ways that cardiac muscle cannot.

Recruitment adds motor units, and units are recruited from smallest to largest — the size principle — so fine control is available at low force.

Summation adds contractions in time. Because the skeletal action potential is far shorter than the twitch, a second stimulus can arrive while the first contraction is still underway, and repeated stimulation fuses the twitches into tetanus.

Cardiac muscle cannot do either, since it has no separate motor units and its long refractory period prevents summation, so it regulates force by changing contractility and preload instead.

Skeletal fibres themselves divide into slow oxidative type I fibres, rich in mitochondria and myoglobin and resistant to fatigue, and fast glycolytic type II fibres, which generate more force but fatigue quickly.

5. Reflexes and the CNS

5.1 Muscle spindle versus Golgi tendon organ

Two receptors monitor muscle, and their arrangement determines what each can sense.

The arrangement is what determines the modality, and this is the reasoning the exam wants.

A receptor lying in parallel is unloaded when the muscle shortens, so it reports length. A receptor lying in series bears whatever force the muscle generates, so it reports tension.

The stretch reflex is the spindle's monosynaptic loop: a tendon tap stretches the muscle, Ia fibres fire, and the alpha motor neuron contracts the same muscle. Reciprocal inhibition simultaneously relaxes the antagonist.

Gamma motor neurons solve a problem the arrangement creates. When the muscle contracts, a parallel spindle would go slack and stop reporting. Gamma neurons contract the spindle's own intrafusal fibres, keeping it taut and sensitive throughout the movement.

The Golgi tendon organ's inhibition is protective, and its exaggeration produces the clasp-knife phenomenon in spasticity, where resistance suddenly gives way once tension rises high enough.

5.2 Upper versus lower motor neuron signs

The distinction is generated by whether descending inhibition survives.

Upper motor neuron lesions leave the final common pathway intact but remove descending inhibition, producing spasticity, hyperreflexia, an extensor plantar response and little wasting.

Lower motor neuron lesions destroy the final pathway itself, producing flaccidity, hyporeflexia, marked wasting and fasciculations.

Fasciculations are the most specific lower motor neuron sign, since they represent spontaneous discharge of a denervated motor unit and cannot occur if the motor neuron is gone entirely.

5.3 Sleep stages and the EEG

Sleep is examinable chiefly through its electroencephalographic signatures.

REM is called paradoxical sleep because the EEG resembles wakefulness while the body is maximally atonic.

Two temporal patterns matter. Slow wave sleep predominates in the first half of the night, and REM periods lengthen towards morning.

That distribution explains a clinical observation: parasomnias arising from deep sleep, such as night terrors, occur early in the night, while vivid nightmares occur towards morning.

7. Common exam traps

• Reversing the fibre vulnerability rules. Local anaesthetics block small fibres first; pressure and hypoxia block large fibres first.
• Confusing myasthenia with Lambert-Eaton. Worsening with activity is postsynaptic; improvement with activity is presynaptic.
• Expecting flaccid paralysis in tetanus. The toxin blocks inhibitory transmitters, so the result is spasticity, unlike botulism.
• Assuming skeletal muscle needs extracellular calcium. It does not; cardiac muscle does, because it uses calcium-induced calcium release.
• Thinking ATP powers the power stroke. ATP is required for detachment, which is why its absence causes rigidity rather than relaxation.
• Mixing up spindle and Golgi tendon organ arrangement. Parallel senses length; in series senses tension.
• Forgetting why gamma motor neurons exist. Without them the spindle would go slack during contraction and stop reporting.
• Placing night terrors in REM sleep. They arise from slow wave sleep, early in the night; REM predominates towards morning.

Summary

• The resting potential sits near the potassium equilibrium potential because resting permeability to potassium dominates, with the sodium-potassium pump maintaining the gradients.
• Sodium channels have separate activation and inactivation gates, and inactivation is what produces the absolute refractory period and unidirectional conduction.
• Conduction velocity rises with diameter and myelination, the latter permitting saltatory conduction.
• Local anaesthetics block small fibres first, so pain is lost before motor power; pressure and hypoxia block large fibres first, so the opposite occurs.
• Transmission requires P/Q calcium channels, quantal acetylcholine release, nicotinic receptor activation and an end-plate potential with a large safety factor.
• Myasthenia gravis is postsynaptic and worsens with activity; Lambert-Eaton is presynaptic and improves with sustained activity.
• Botulinum toxin prevents acetylcholine release and causes flaccid descending paralysis; tetanus toxin blocks inhibitory transmitters and causes spasticity.
• In skeletal muscle the dihydropyridine receptor is mechanically coupled to the ryanodine receptor, so no extracellular calcium is needed.
• In cardiac muscle the dihydropyridine receptor admits calcium that triggers further release, so contraction depends on extracellular calcium.
• Calcium binds troponin C in striated muscle, while smooth muscle uses calcium-calmodulin to activate myosin light chain kinase.
• ATP is needed to detach myosin from actin, which is why its depletion after death produces rigor mortis, and relaxation requires the SERCA pump.
• The muscle spindle lies in parallel and senses length through Ia afferents in a monosynaptic reflex; the Golgi tendon organ lies in series and senses tension through Ib afferents with disynaptic inhibition.
• Gamma motor neurons keep the spindle taut during contraction so it continues to report length.
• Upper motor neuron lesions give spasticity and hyperreflexia from lost descending inhibition; lower motor neuron lesions give flaccidity, wasting and fasciculations.
• EEG stages run beta when alert, alpha with eyes closed, theta in N1, spindles and K complexes in N2, delta in N3, and a desynchronised pattern in REM.
• Slow wave sleep dominates the first half of the night and hosts the parasomnias, while REM periods lengthen towards morning.