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PY3.1-12 | Nerve and Muscle Physiology — SDL Guide

Learning Objectives

• Describe the structure and function of a neuron and classify neurons by structure and function (PY3.1)
• Explain the ionic basis of the resting membrane potential using the Nernst and Goldman equations (PY3.2)
• Describe the genesis of the action potential, its ionic basis, and the properties of nerve fibres (PY3.3)
• Explain the classification of nerve fibres based on diameter and conduction velocity (PY3.4)
• Describe synaptic transmission — electrical and chemical synapses, neurotransmitter release and receptor mechanisms (PY3.5)
• Describe the structure and function of the neuromuscular junction and the molecular basis of neuromuscular transmission (PY3.6)
• Explain the molecular mechanism of skeletal muscle contraction — excitation-contraction coupling and the sliding filament theory (PY3.7)
• Describe the types of skeletal muscle fibres and their functional significance (PY3.8)
• Explain the properties of skeletal muscle — twitch, tetanus, summation, and the length-tension relationship (PY3.9)
• Describe the structure and mechanism of contraction of smooth muscle and compare it with skeletal muscle (PY3.10)
• Describe the structure and mechanism of contraction of cardiac muscle and compare it with skeletal and smooth muscle (PY3.11)
• Explain the energy metabolism of muscle — sources of ATP, oxygen debt, and fatigue (PY3.12)

INSTRUCTIONS

This module covers the physiology of nerve and muscle — the electrical and mechanical systems that make all movement possible. We'll build from the resting membrane potential through the action potential, nerve conduction, synaptic transmission, the neuromuscular junction, and finally the molecular machinery of muscle contraction.

Parallel connections: In Anatomy, you're dissecting the muscles of the upper limb — the muscles you study there are the same ones whose physiology we explore here. When you identify biceps brachii on a cadaver, you're looking at bundles of skeletal muscle fibres that contract by the sliding filament mechanism you'll learn in Part 2. In Biochemistry, the calcium and sodium ions that drive nerve impulses are the same minerals and electrolytes you're studying — and the extracellular matrix (ECM) you're learning about provides the structural scaffolding around every nerve and muscle fibre.

References

• Guyton and Hall Textbook of Medical Physiology, 14th ed., Chapters 5–9: Membrane Potentials, Action Potentials, Skeletal Muscle, Cardiac Muscle, Smooth Muscle (textbook)
• Ganong's Review of Medical Physiology, 26th ed., Chapters 4–5: Excitable Tissue (Nerve & Muscle) (textbook)
• OpenStax Anatomy and Physiology 2e, Chapters 12.4–12.5 (Nerve Impulse) and Chapter 10 (Muscle Tissue) (textbook (CC BY 4.0))
• B.D. Chaurasia's Human Anatomy, Vol. 1 — Upper Limb (parallel anatomy reference) (textbook)

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Version 2.0 | NMC CBUC 2024, Adapted from OpenStax A&P 2e (CC BY 4.0)

The Neuron — Structure and Classification (PY3.1)

The neuron (nerve cell) is the functional unit of the nervous system. It's specialised for generating and transmitting electrical signals.

Figure: The Neuron — Structure and Classification (PY3.1)

Structure of a typical neuron:
• Cell body (soma) — contains the nucleus, rough endoplasmic reticulum (Nissl bodies), mitochondria, and the metabolic machinery. This is the 'command centre' where most protein synthesis occurs.
• Dendrites — short, branching processes that receive signals from other neurons. They increase the surface area for synaptic input.
• Axon — a single, long process that conducts the action potential away from the cell body. It begins at the axon hillock (the 'trigger zone' where action potentials are initiated). The axon may be myelinated (wrapped in Schwann cells in the PNS or oligodendrocytes in the CNS) or unmyelinated.
• Axon terminals (synaptic boutons) — the branched endings of the axon that form synapses with target cells.

Classification by structure:
• Multipolar — one axon, many dendrites (most common; motor neurons, interneurons)
• Bipolar — one axon, one dendrite (retina, olfactory epithelium, vestibular ganglion)
• Unipolar (pseudounipolar) — single process that splits into two branches (dorsal root ganglion sensory neurons)

Classification by function:
• Sensory (afferent) — carry signals from receptors to the CNS
• Motor (efferent) — carry signals from the CNS to effectors (muscles, glands)
• Interneurons — connect neurons within the CNS; form circuits

Supporting cells (neuroglia): Neurons don't work alone. Schwann cells myelinate PNS axons (one Schwann cell = one internode). Oligodendrocytes myelinate CNS axons (one oligodendrocyte = multiple internodes). Astrocytes maintain the blood-brain barrier and regulate ion/neurotransmitter concentrations. Microglia are the immune cells of the CNS.

The Resting Membrane Potential (PY3.2)

Every living cell has a voltage difference across its membrane. In neurons and muscle cells, this voltage is called the resting membrane potential (RMP), and it's typically about -70 mV (the inside of the cell is negative relative to the outside).

Figure: The Resting Membrane Potential (PY3.2)

Why does the RMP exist? Three factors:

1. Unequal ion distribution:
• K+ is concentrated INSIDE the cell (~140 mM inside, ~4 mM outside)
• Na+ is concentrated OUTSIDE the cell (~140 mM outside, ~14 mM inside)
• Large anions (A-) — proteins and organic phosphates are trapped inside the cell and cannot cross the membrane

2. Selective membrane permeability:
At rest, the membrane is ~50–100 times more permeable to K+ than to Na+. This is because there are many more K+ leak channels open at rest than Na+ channels. K+ therefore diffuses OUT of the cell, down its concentration gradient, taking positive charge with it — leaving the inside negative.

But K+ can't keep leaving forever. As positive charge leaves, the inside becomes negative, creating an electrical gradient that pulls K+ back in. Eventually, the chemical gradient (pushing K+ out) exactly balances the electrical gradient (pulling K+ back in). This equilibrium voltage is the Nernst potential for K+ (E_K).

The Nernst Equation:
E_ion = (RT/zF) × ln([ion]_outside / [ion]_inside)

At body temperature (37°C), simplified:
E_ion = (61.5/z) × log₁₀([ion]_outside / [ion]_inside)

• E_K = 61.5 × log(4/140) = -94 mV
• E_Na = 61.5 × log(140/14) = +61 mV

3. The Na+/K+-ATPase pump:
This pump actively transports 3 Na+ out and 2 K+ in per ATP hydrolysed. It's electrogenic (net export of positive charge) and contributes about -3 to -5 mV to the RMP. More importantly, it maintains the ion gradients that the RMP depends on.

The Goldman Equation (Goldman-Hodgkin-Katz equation):
The actual RMP is not exactly at E_K because the membrane has some permeability to Na+ and Cl-. The Goldman equation accounts for all permeable ions:

V_m = (RT/F) × ln[(P_K[K+]_o + P_Na[Na+]_o + P_Cl[Cl-]_i) / (P_K[K+]_i + P_Na[Na+]_i + P_Cl[Cl-]_o)]

Since P_K >> P_Na at rest, the RMP (~-70 mV) is close to E_K (-94 mV) but slightly less negative because of the small inward Na+ leak.

Clinical significance: Hyperkalaemia (high plasma K+) is dangerous because it reduces the K+ concentration gradient, making the RMP less negative (depolarised). This brings the membrane closer to threshold and can cause cardiac arrhythmias. Hypokalaemia hyperpolarises the membrane, making cells less excitable.

The Action Potential — Generating Electricity (PY3.3)

The action potential (AP) is a rapid, transient reversal of the membrane potential — from -70 mV to about +30 mV and back — lasting about 1-2 ms in nerve. It's the signal that carries information along nerves and triggers muscle contraction.

Figure: The Action Potential — Generating Electricity (PY3.3)

Phases of the action potential:

1. Resting state (-70 mV): Voltage-gated Na+ channels are CLOSED (but can be opened). Voltage-gated K+ channels are CLOSED. Only leak channels are open.

2. Depolarisation to threshold (-55 mV): A stimulus (from a synapse, a receptor, or a neighbouring AP) opens some Na+ channels. Na+ flows in, making the inside less negative. If the depolarisation reaches threshold (~-55 mV), voltage-gated Na+ channels open explosively.

3. Rapid depolarisation (rising phase, -55 → +30 mV): Voltage-gated Na+ channels open — Na+ rushes in (Na+ permeability increases ~600-fold). Positive feedback: more Na+ in → more depolarisation → more Na+ channels open. The membrane potential races toward E_Na (+61 mV) but doesn't quite reach it because...

4. Repolarisation (falling phase, +30 → -70 mV): Two events occur simultaneously:
• Na+ channels inactivate — the inactivation gate (h gate) closes, stopping Na+ influx. This happens automatically ~0.5 ms after the channel opens.
• Voltage-gated K+ channels open (they're slow to respond). K+ rushes OUT, restoring the negative interior.

5. Hyperpolarisation (undershoot, to -80 mV): K+ channels are slow to close, so K+ keeps flowing out briefly, making the membrane more negative than the RMP. This is the after-hyperpolarisation.

6. Return to rest: K+ channels close, Na+/K+-ATPase restores ion gradients, RMP returns to -70 mV.

Key properties of the action potential:
• All-or-none law — once threshold is reached, the AP fires at full amplitude. Below threshold, no AP. There's no partial AP.
• Refractory periods:
- Absolute refractory period — Na+ channels are inactivated; no stimulus, however strong, can generate another AP. This limits the maximum firing frequency (~1000 Hz) and ensures unidirectional propagation.
- Relative refractory period — some Na+ channels have recovered; a stronger-than-normal stimulus can generate an AP (but it's smaller). This corresponds to the hyperpolarisation phase.
• Threshold — the critical depolarisation needed to trigger the regenerative opening of voltage-gated Na+ channels (~-55 mV in most neurons).

Spiral forward: In Pharmacology, you'll learn how local anaesthetics (lidocaine) block voltage-gated Na+ channels, preventing AP generation — the molecular basis of numbing pain.

Nerve Fibre Classification and Conduction Velocity (PY3.4)

Once an action potential is generated, it must travel along the nerve fibre (axon) to reach its target. The speed of this conduction varies enormously — from 0.5 m/s to 120 m/s — depending on two factors: myelination and fibre diameter.

Conduction in unmyelinated fibres — continuous conduction:
The AP at one point depolarises the adjacent membrane by local current flow, which triggers a new AP at the next point. This proceeds point-by-point along the entire length of the axon. It's slow because the entire membrane must be depolarised sequentially.

Conduction in myelinated fibres — saltatory conduction:
Myelin acts as an insulator, preventing current flow across the membrane at myelinated segments (internodes). Ion channels are concentrated at the nodes of Ranvier — small gaps between myelin segments. The AP 'jumps' from node to node (Latin: saltare = to jump). This is much faster because:
1. Only the nodes need to depolarise (not the entire membrane)
2. Current flows rapidly through the myelinated internodes by electrotonic (cable) conduction

Erlanger-Gasser classification (by conduction velocity):

Type	Diameter	Velocity	Myelinated	Function
Aα	12–20 μm	70–120 m/s	Yes (heavy)	Motor to skeletal muscle, proprioception
Aβ	5–12 μm	30–70 m/s	Yes	Touch, pressure
Aγ	3–6 μm	15–30 m/s	Yes	Motor to muscle spindles
Aδ	2–5 μm	12–30 m/s	Yes (light)	Fast pain, temperature, crude touch
B	<3 μm	3–15 m/s	Yes (light)	Preganglionic autonomic
C	0.4–1.2 μm	0.5–2 m/s	No	Slow pain, postganglionic autonomic

Clinical significance:
• Local anaesthetics block small, unmyelinated C fibres first (pain) before larger myelinated fibres (touch, motor) — this is why you lose pain sensation before touch during a nerve block.
• Demyelinating diseases (multiple sclerosis, Guillain-Barré syndrome) slow or block conduction because they disrupt saltatory conduction. The nerve still has its axons, but without myelin, conduction is devastatingly slow.
• The nerve conduction study (NCS) measures conduction velocity clinically — a key diagnostic tool for peripheral neuropathies.