2. Electrical Signalling & Synaptic Transmission

Overview

Neurons are specialised, excitable cells designed for rapid, one-way communication.
Communicate by converting electrical signals (action potentials, APs) into chemical signals (neurotransmitters, NTs) and back again.

Functional polarity describes the unidirectional flow of information within a neuron and between neurons. Information is consistently received by the dendrites, which function as the receptive zone of the neuron. From the dendrites, the electrical signals are transmitted to the soma, or cell body, where integration of these signals occurs. Following processing in the soma, the integrated signal travels down the axon, which serves as the conductive zone. Upon reaching the axon terminals, specialized structures at the end of the axon, the neuron acts as a secretory zone, releasing neurotransmitters into the synapse. The synapse is the crucial junction where these chemical signals are transmitted to the next cell in the neural pathway. This ensures a consistent and directional flow of information throughout the nervous system.

Multiple neurons are chained together to span long distances (e.g. brain → spinal cord → foot).
Axon length & cell-body placement vary to minimise space (e.g. long peripheral axon with soma off to the side vs. short intracranial axon).

Electrical vs Chemical Signalling

Electrical: within a neuron (membrane potentials & APs).
Chemical: between cells at the synapse (NT release).
Region terms:
• Pre-synaptic = before synapse (sending cell).
• Post-synaptic = after synapse (receiving cell).

Three Key Events in Neuronal Communication

Generate the AP (depolarisation).
Conduct the AP along axon.
Synaptic transmission (chemical → electrical in next cell).

Membrane Potential (MP) Basics

Definition: charge difference across plasma membrane.
All cells have an MP; only neurons & muscle can change it rapidly.
At rest the inside is negative relative to outside (≈ $-70\ \text{mV}$ in neurons).

Ionic Environment

Fluids are isotonic (equal total solute) but differ in individual ions.
• Inside (ICF): high $K^+$ , low $Na^+$ , many negatively charged proteins ( $A^-$ ).
• Outside (ECF): high $Na^+$ , low $K^+$ , $Cl^-$ plentiful.
Ion movement requires membrane proteins because lipid bilayer blocks charged particles.

Ion Channels

Selective (e.g. $K^+$ channel, $Na^+$ channel) or non-selective cation channels.
Opening → increases permeability for that ion, allowing diffusion down its concentration gradient.

Establishing Resting MP

At rest:
• Many leak $K^+$ channels are OPEN → $K^+$ diffuses out, taking + charge with it.
• Most $Na^+$ channels are CLOSED → little Na⁺ influx.
• Result: net positive charge accumulates just outside membrane, leaving inside negative.
Na⁺/K⁺ ATPase (pump) maintains gradients: pumps 3 $Na^+$ out & 2 $K^+$ in using ATP (active transport) to reset concentrations long-term.

MP Changes & Electrical Signals

Depolarisation: MP becomes less negative/positive.
• Open $Na^+$ channels ⇒ $Na^+$ rushes in (↑ positivity) ⇒ MP moves toward $0$ & beyond.
Repolarisation: return to resting negativity.
• Close $Na^+$ channels, open $K^+$ channels ⇒ $K^+$ exits, removing + charge.
Hyperpolarisation: MP becomes more negative than resting (e.g. $-90\ \text{mV}$ ).
• Open extra $K^+$ channels or open $Cl^-$ channels (Cl⁻ enters) ⇒ inhibitory, harder to fire AP.

Action Potential (AP) Generation

Triggered when depolarisation reaches threshold (≈ $-55\ \text{mV}$ ).
All-or-none: once begun, amplitude is constant.
Events:
1. Rapid $Na^+$ influx (voltage-gated $Na^+$ channels) ⇒ sharp depolarisation.
2. Inactivation of $Na^+$ channels + opening of voltage-gated $K^+$ channels ⇒ repolarisation.
3. Brief $K^+$ overshoot ⇒ after-hyperpolarisation.
4. Na⁺/K⁺ pump restores ionic gradients.

AP Conduction Along Axon

Opening of channels is sequential: depolarisation at one segment brings adjacent segment to threshold ("Mexican wave").
Unidirectional because channels behind the wave are transiently inactivated (refractory period).

Myelination & Saltatory Conduction

Myelin (lipid sheath by oligodendrocytes CNS / Schwann cells PNS) prevents ion leakage.
Gaps = Nodes of Ranvier where voltage-gated $Na^+$ channels cluster.
Local current leaps node-to-node (saltatory) ⇒ fewer openings, faster transmission.
Demyelination (e.g. Multiple Sclerosis):
• ↑ ion leak, ↓ conduction velocity, conduction block, neurological deficits.

Synaptic Transmission

Synapse = junction between presynaptic axon terminal & postsynaptic membrane, separated by synaptic cleft (~20–40 nm).

Three Fundamental Steps

AP arrival & Ca²⁺ entry
- AP depolarises axon terminal → voltage-gated $Ca^{2+}$ channels open.
- Extracellular $Ca^{2+}$ (high outside) floods in.
NT release (exocytosis)
- $Ca^{2+}$ triggers synaptic vesicle fusion with membrane.
- NT molecules released into cleft.
Postsynaptic effect
- NT binds receptors → opens/closes ion channels.
- EPSP (excitatory, usually $Na^+$ entry) or IPSP (inhibitory, $K^+$ out or $Cl^-$ in).
- If local depolarisation reaches threshold at axon hillock, new AP fires in postsynaptic neuron.

Terminating NT Action (3 ways)

Diffusion out of cleft.
Enzymatic degradation (e.g. acetylcholinesterase hydrolyses ACh).
Reuptake into presynaptic terminal or surrounding glia (astrocytes).

Clinical / Functional Connections

Hyperpolarisation as inhibition used for muscle relaxation & signal gating.
Many drugs/toxins target:
• Ion channels (local anaesthetics block $Na^+$ channels).
• NT reuptake (SSRIs inhibit serotonin reuptake).
• Enzymes (neostigmine blocks AChE).
Demyelinating diseases slow/stop conduction → motor & sensory deficits.

Study Tips

Master ion distributions first ("Na⁺ out, K⁺ in").
Use coloured counters/M&Ms to simulate charge movement for depolarisation vs hyperpolarisation.
Sketch graphs of MP vs time (label phases, ion movements).
Memorise the "rule of threes":
• 3 Na⁺ out / 2 K⁺ in (pump).
• 3 events for AP (generate, conduct, synaptic transmission).
• 3 steps of chemical synapse.
• 3 NT termination mechanisms.