Human Physiology

• Cell body (soma): contains nucleus and most organelles
• Dendrites: receive impulses from other neurons
• Axon: long fibre that transmits impulses away from the cell body
• Myelin sheath: insulating fatty layer (Schwann cells in PNS); speeds up transmission
• Nodes of Ranvier: gaps in the myelin sheath; allow saltatory conduction (impulse "jumps" between nodes)
• Axon terminal (synaptic knob): releases neurotransmitters at the synapse

When a neuron is not transmitting an impulse, it has a resting potential of approximately −70 mV (inside is negative relative to outside).

How It Is Maintained

• Sodium-potassium pump ($Na^+/K^+$ ATPase): actively transports 3 Na⁺ out and 2 K⁺ in per cycle (using ATP)
• K⁺ leak channels: K⁺ diffuses out down its concentration gradient (more K⁺ inside than outside)
• The net effect: more positive ions outside than inside → membrane is polarised (−70 mV)

An action potential is a brief reversal of the resting potential that propagates along the axon.

Stages

1. Resting state (−70 mV): Na⁺ channels closed; K⁺ leak channels open; Na⁺/K⁺ pump maintaining potential
2. Depolarisation: A stimulus reaches threshold (−55 mV) → voltage-gated Na⁺ channels open → Na⁺ rushes INTO the cell → membrane potential rises rapidly to about +30 mV
3. Repolarisation: Na⁺ channels close (inactivate); voltage-gated K⁺ channels open → K⁺ rushes OUT → potential drops back towards −70 mV
4. Hyperpolarisation: K⁺ channels close slowly → potential temporarily drops below −70 mV (about −80 mV)
5. Recovery: Na⁺/K⁺ pump restores resting potential (−70 mV)

Key Principles

• Threshold: minimum stimulus needed to trigger an action potential (−55 mV)
• All-or-nothing: action potentials always have the same amplitude (if threshold is reached, a full action potential fires; if not, nothing happens)
• Refractory period: brief period after an action potential when the neuron cannot fire again; ensures one-way propagation and limits firing frequency

• Local currents: depolarisation of one section of the axon triggers the next section
• In unmyelinated axons: impulse travels continuously along the membrane (slow, ~1 m/s)
• In myelinated axons: impulse jumps between Nodes of Ranvier (saltatory conduction) — much faster (~100 m/s)
• Speed also depends on axon diameter (larger = faster)

A synapse is the junction between two neurons (or between a neuron and an effector).

Steps of Chemical Synaptic Transmission

1. An action potential arrives at the presynaptic terminal (synaptic knob)
2. Voltage-gated Ca²⁺ channels open → Ca²⁺ ions flow into the terminal
3. Ca²⁺ causes synaptic vesicles (containing neurotransmitter, e.g., acetylcholine) to move to and fuse with the presynaptic membrane
4. Neurotransmitter is released into the synaptic cleft by exocytosis
5. Neurotransmitter diffuses across the cleft and binds to receptors on the postsynaptic membrane
6. This binding opens ligand-gated ion channels (e.g., Na⁺ channels) → ions flow in → depolarisation of the postsynaptic membrane
7. If threshold is reached → new action potential in the postsynaptic neuron
8. Neurotransmitter is rapidly removed from the cleft:
   • Enzymatic breakdown (e.g., acetylcholinesterase breaks down acetylcholine)
   • Reuptake into the presynaptic neuron
   • Diffusion away from the cleft

Excitatory vs Inhibitory Synapses

• Excitatory: neurotransmitter opens Na⁺ channels → depolarisation → promotes action potential
• Inhibitory: neurotransmitter opens Cl⁻ or K⁺ channels → hyperpolarisation → inhibits action potential
• Whether the postsynaptic neuron fires depends on the sum of excitatory and inhibitory inputs (summation)

Neonicotinoids (IB-specific example)

• Insecticides that bind to acetylcholine receptors in insect nervous systems
• They are not broken down by acetylcholinesterase → persistent stimulation → paralysis → death
• Concern: harmful to pollinators (bees) → some countries have restricted their use

Drugs can affect synaptic transmission in various ways:

Question: Describe the events occurring at a cholinergic synapse when an impulse arrives. (6 marks)

Solution: When an action potential arrives at the presynaptic terminal, voltage-gated calcium ion channels open and $Ca^{2+}$ ions diffuse into the knob. The influx of calcium causes synaptic vesicles containing acetylcholine (ACh) to fuse with the presynaptic membrane and release ACh into the synaptic cleft by exocytosis. ACh diffuses across the cleft and binds to complementary receptors on the postsynaptic membrane. This opens sodium ion channels, allowing Na⁺ to flow into the postsynaptic neuron, causing depolarisation. If the depolarisation reaches threshold, a new action potential is generated. ACh is then broken down by acetylcholinesterase into acetyl and choline, which are reabsorbed into the presynaptic neuron for re-synthesis of ACh.

• Resting potential (−70 mV): maintained by Na⁺/K⁺ pump and K⁺ leak channels.
• Action potential: threshold → Na⁺ in (depolarisation) → K⁺ out (repolarisation) → recovery. All-or-nothing.
• Myelination enables saltatory conduction (faster impulse transmission).
• Synaptic transmission: action potential → Ca²⁺ influx → vesicle fusion → neurotransmitter release → receptor binding → postsynaptic depolarisation → neurotransmitter removal.
• Drugs affect synapses by mimicking, blocking, or altering neurotransmitter levels.