Electrical Signalling & Synaptic Transmission in Neurons

Neuron Types & Structural Organization

Neurons are specialized for communication (information sensing, integration, motor output).
Same basic parts: dendrites (receptive zone), soma/cell body (integration), axon (conducting zone), axon terminals (transmitting zone).
Layout is adapted to distance:
- Brain interneurons: short axon; soma close to dendrites & terminals (short path across brain).
- Peripheral motor/sensory neurons: extremely long axon; cell body may sit off to the side to avoid bulky limbs (e.g.
  spinal cord ➜ foot).
Always ONE-WAY flow: dendrites ➜ soma ➜ axon ➜ terminals.
Messages from brain to muscle usually require several neurons chained together (relay of identical events in each neuron).

Electrical vs. Chemical Signalling

Electrical signalling: movement of ionic charge within a neuron (action potentials).
Chemical signalling: neurotransmitter release across synapses to the next cell (neuron, muscle, gland).
Synapse = junction where electrical ➜ chemical ➜ electrical conversion occurs.
Terminology:
• Presynaptic neuron: sends AP and releases transmitter.
• Postsynaptic neuron/effector: receives transmitter and responds.

Three Key Events in Neuronal Communication

Generate an action potential (AP) – involves depolarisation.
Conduct the AP along the axon (propagation).
Synaptic transmission – convert AP to neurotransmitter release, interact with next cell.

Membrane Potential Fundamentals

Membrane potential (Vm): charge difference between intracellular fluid (ICF) and extracellular fluid (ECF) right across the plasma membrane.
Convention: Outside set to $0$ ; Vm expresses how inside differs (usually negative).
Simple charge-count example: 3 positives outside vs 3 negatives inside gives $(-3 \to +3) ⇒ \Delta = 6$ ; Vm reported as $-6$ (inside more negative by 6 units).
All body fluids are isotonic (equal total solute), but individual ion concentrations differ:
- ICF: high $\text{K}^+$ , proteins (−).
- ECF: high $\text{Na}^+$ & $\text{Cl}^-$ .
Lipid bilayer blocks ions; movement requires ion channels or transporters.

Leak Channels & Resting Potential

At rest: many $\text{K}^+$ leak channels OPEN, most $\text{Na}^+$ channels CLOSED.
$\text{K}^+$ diffuses out (down gradient) carrying + charge ➜ inside becomes negative (~ $-70 \text{ mV}$ ).
$\text{Na}^+/\text{K}^+$ ATPase (exchange pump) maintains gradients: $3\ \text{Na}^+<em>{out} : 2\ \text{K}^+</em>{in}$ per ATP (active transport).

Depolarisation, Repolarisation, Hyperpolarisation

Depolarisation: Vm moves toward $0$ then positive.
• Mechanism: open $\text{Na}^+$ channels ➜ $\text{Na}^+$ influx (positive charge enters).
Repolarisation: return to resting negative Vm.
• Close $\text{Na}^+$ channels, open $\text{K}^+$ channels ➜ $\text{K}^+$ efflux, pump restores original ion distribution.
Hyperpolarisation: Vm becomes MORE negative than rest (e.g. $-90 \text{ mV}$ ).
• Open extra $\text{K}^+$ channels or open $\text{Cl}^-$ channels (negative enters).
• Makes it harder to reach threshold: larger change required to depolarise.

Action Potential Conduction (Axon)

Trigger zone (axon hillock/initial segment) loaded with voltage-gated $\text{Na}^+$ channels.
AP propagation = sequential opening of channels like a Mexican wave.
Unidirectionality: recently opened channels enter brief inactivated state ➜ cannot reopen immediately.

Myelination & Saltatory Conduction

Myelin (lipid sheath: oligodendrocytes CNS / Schwann PNS) blocks ion leakage.
$\text{K}^+$ can’t leak through myelin ➜ current spreads internally to next node of Ranvier.
Voltage-gated $\text{Na}^+$ channels clustered only at nodes ➜ AP "jumps" node-to-node (saltatory conduction).
Result: far fewer channel openings, greatly increased speed.
Demyelination (e.g. multiple sclerosis): current lost, nodes too far apart, signal fails or is delayed.

Synaptic Transmission (Chemical Step)

AP reaches axon terminal; voltage-gated $\text{Ca}^{2+}$ channels open.
$\text{Ca}^{2+}$ influx triggers vesicle fusion ➜ neurotransmitter exocytosis into synaptic cleft.
Neurotransmitter binds postsynaptic receptors ➜ ion channels open/close:
- If $\text{Na}^+$ or other cation channel opens ➜ excitatory postsynaptic potential (EPSP), depolarises cell; AP likely.
- If $\text{K}^+$ opens or $\text{Cl}^-$ enters ➜ inhibitory postsynaptic potential (IPSP), hyperpolarises; AP suppressed.

Termination of Neurotransmitter Action (Three Ways)

Diffusion away from cleft.
Re-uptake into presynaptic terminal (transporters).
Enzymatic breakdown in cleft; products then taken up (e.g. acetylcholinesterase acting on ACh).

Chains of Synapses in Pathways

Brain ➜ spinal cord ➜ motor neuron ➜ muscle is multi-synaptic; each synapse introduces potential modulation (excitation, inhibition).
Total outcome (movement, relaxation, secretion) depends on integration of all EPSPs & IPSPs on postsynaptic neuron.

Clinical & Real-World Connections

Muscle relaxation can result from inhibitory neurotransmission at final motor synapse.
Pharmacology targets:
• Block $\text{Na}^+$ channels (local anaesthetics) ➜ stop AP generation.
• Modulate re-uptake/enzymes (antidepressants, cholinesterase inhibitors).
• Enhance/inhibit $\text{Cl}^-$ channels (benzodiazepines, epilepsy drugs).
Demyelinating diseases disrupt conduction ➜ sensory/motor deficits.

Analogies & Study Tips

Number-line: outside $=0$ , inside value shows polarity.
M&Ms: use colours to represent $\text{Na}^+$ , $\text{K}^+$ , charges; physically move to visualise depolarisation/repolarisation.
Mexican wave: illustrates sequential channel opening.
Small vs big steps: continuous vs saltatory conduction speed comparison.

Summary of Key "Threes"

3 main events in neuronal signalling: Generate AP ➜ Conduct AP ➜ Synaptic transmission.
3 steps in synaptic transmission:
1. AP & $\text{Ca}^{2+}$ entry.
2. Neurotransmitter release.
3. Postsynaptic receptor action.
3 ways to terminate transmitter: diffusion, re-uptake, enzymatic breakdown.

Understanding ion distribution, channel behaviour, and conversion between electrical & chemical messages is essential for explaining normal neural function, disease mechanisms, and many therapeutic interventions.