Neuronal Physiology and Synaptic Transmission

Evolutionary Theme: Simplicity & Re-use

• Biological systems often recycle the same mechanisms in many cell types (neurons, kidney, heart, etc.).

• The ubiquitous example in this lecture: the Sodium–Potassium (Na⁺/K⁺) ATPase pump.

The Sodium–Potassium Pump (Na⁺/K⁺-ATPase)

• Always active; powered by ATP.

• Stoichiometry per cycle:

  • 3 Na⁺ pumped out of the cell.

  • 2 K⁺ pumped into the cell.

• Net effect: loss of one positive charge from cytoplasm each cycle → cell interior becomes more negative.

• Analogy: Bank account

  • Withdraw 3, deposit 2 → balance -1.

  • Repeated cycles drop the “charge balance” by 1 each time.

• Creates & maintains

  • High [Na⁺] outside, low [Na⁺] inside.

  • High [K⁺] inside, low [K⁺] outside.

  • Resting membrane potential ≈ -70\;\text{mV}.

• Other contributors to negativity: negatively charged intracellular proteins.

Resting Membrane Potential (RMP)

• Definition: Baseline electrical charge difference across plasma membrane when the neuron is inactive.

• Typical value: -70\;\text{mV}.

Ion Movement & Diffusion Principles

• Ions move passively via diffusion: from high → low concentration.

• Because ions are charged, they cannot cross lipid bilayer unaided; need channels.

Types of Ion Channels (“Doors” in Membrane)

1. Leak (non-gated) channels – always open; provide constant permeability.

2. Mechanically-gated channels – open when membrane is physically deformed (e.g., touch receptors).

3. Voltage-gated channels – open/close in response to changes in membrane voltage (e.g., Na⁺ & K⁺ channels that drive action potentials).

4. Ligand-gated channels – open when a chemical (ligand) binds (e.g., neurotransmitter-gated Na⁺ channels at synapses).

• Joke flavors mentioned: “chocolate, strawberry, vanilla” → emphasizes 4 “real” types.

Action Potentials (AP) – The “Stadium Wave”

• All-or-none electrical events propagating along axon.

• Phases illustrated with Na⁺ & K⁺ channel dynamics:

  1. Depolarization – Voltage-gated Na⁺ channels open; Na⁺ rushes in → interior becomes more positive.

  • Example: add +1 to -70 → -69, repeating until ~+35\;\text{mV} peak.

  1. Repolarization – Voltage-gated K⁺ channels open; K⁺ leaves cell → interior regains negativity.

  • Can overshoot (hyperpolarize) slightly past -70\;\text{mV}.

• Threshold of excitation: -55\;\text{mV}.

  • Below threshold: no AP;

  • Reaching threshold → guaranteed full-size AP.

• No “half” APs; strength coded by frequency/pattern, not amplitude.

Myelination & Saltatory Conduction

• Myelin = insulating lipid sheath; gaps called Nodes of Ranvier.

• AP “jumps” node-to-node → saltatory conduction (Latin saltare = to jump; cf. “somersault”).

• Increases conduction velocity; example comparison:

  • Pain fibers (fast) vs. other slower unmyelinated fibers.

• Tape-dispenser analogy: passing dispenser directly to end of row faster than person-to-person.

Synapse Anatomy & Variants

• Synaptic cleft: 20–40 nm gap; no physical continuity.

• Common synapse types (ranked by prevalence):

  1. Axodendritic – axon → dendrite (most common).

  2. Axosomatic – axon → soma.

  3. Axoaxonic – axon → axon/initial segment/node.

  4. Dendrodendritic – dendrite → dendrite (rare, poorly understood).

• Human brain estimates:

  • ≈ 86 \times 10^{9} neurons.

  • Each neuron average ≈ 7 000 synapses (some far more).

Graded Potentials & Neural “Tug of War”

• Occur in dendrites & soma; vary in size; decay with distance/time.

• Two flavors:

  • EPSP (Excitatory Post-Synaptic Potential) – depolarizing, brings membrane toward threshold (e.g., +Na⁺ in).

  • IPSP (Inhibitory Post-Synaptic Potential) – hyperpolarizing, drives membrane away from threshold (e.g., +Cl⁻ in or K⁺ out).

• Summation at axon hillock (integrating zone):

  • Spatial: multiple synapses active simultaneously.

  • Temporal: rapid, successive inputs from one synapse.

• Tug-of-war analogy:

  • 4 people (EPSPs) pull toward AP; 2 people (IPSPs) pull against.

  • Net result decides if membrane reaches -55\;\text{mV}.

Seven-Step Chemical Synaptic Transmission

1. AP arrives at presynaptic axon terminal.

2. Depolarization opens voltage-gated Ca²⁺ channels in terminal membrane.

3. Ca²⁺ influx (diffuses down gradient) into terminal.

4. Ca²⁺ triggers vesicle fusion with presynaptic membrane (exocytosis).

   • Vesicles contain neurotransmitter (ACh, dopamine, serotonin, GABA, glutamate, etc.).

5. Neurotransmitter diffuses across synaptic cleft and binds ligand-gated ion channels on postsynaptic membrane.

   • Example shown: ligand-gated Na⁺ channel.

6. Channels open → Na⁺ influx into postsynaptic neuron (down its gradient).

7. Postsynaptic depolarization; if cumulative EPSPs reach -55\;\text{mV} threshold → new AP generated.

Key Numerical Benchmarks

• Resting membrane potential: V_{rest} \approx -70\;\text{mV}.

• Threshold potential: V_{th} \approx -55\;\text{mV}.

• AP peak: \approx +35\;\text{mV}.

• Na⁺/K⁺ pump stoichiometry: 3\,\text{Na}^+{out} : 2\,\text{K}^+{in} per ATP.

• Neuron count: \approx 8.6 \times 10^{10}.

• Avg synapses/neuron: \sim 7 \times 10^{3}.

Illustrative Metaphors & Examples

• Bank withdrawal/deposit to explain pump charge balance.

• Stadium wave to illustrate propagation of depolarization/repolarization.

• Tug of war for EPSP vs. IPSP summation.

• Tape-dispenser throw to visualize saltatory conduction speed advantages.

• Chocolate/strawberry/vanilla joke to lighten the 4-channel types.

Practical & Clinical Relevance

• Ion gradients essential for neuronal communication, muscle contraction, kidney function, etc.

• Malfunctioning Na⁺/K⁺ pumps or myelin loss (e.g., multiple sclerosis) disrupt neural signaling.

• Understanding ligand-gated channels underpins pharmacology of neurotransmitters, drugs, toxins.

• Voltage-gated Ca²⁺ channels are therapeutic targets for pain, hypertension.

Connections to Future Lectures

• Ligands in endocrine system (hormones) vs. neurotransmitters in nervous system.

• Mechanically-gated channels reappear in sensory physiology (touch, hearing).

• Voltage-gated channels central to cardiac action potentials.