CM06 - Action Potential

Biomedical Sciences I

What is excitability?

The ability of certain cells (neurons, muscle cells) to rapidly alter ion permeability upon stimulation, changing Vm.

What is a graded potential?

A small, local change in Vm (depolarizing or hyperpolarizing), proportional to stimulus strength, decremental with distance.

What is an action potential (AP)?

A rapid depolarization/repolarization cycle triggered when threshold Vm is reached; all-or-none; identical amplitude in excitable cells.

What happens when a Na+ channel opens?

Na+ enters the cell → depolarization.

What happens when a K+ channel opens?

K+ leaves the cell → hyperpolarization. If closed, prevents K+ efflux.

What happens when a Ca2+ channel opens?

Ca2+ enters the cell → depolarization.

What happens when a Cl- channel opens?

Cl- enters the cell (or leaves depending on gradient) → usually hyperpolarization.

What activates voltage-gated ion channels?

A change in Vm that reaches threshold potential.

What stimuli can induce graded potentials?

Neurotransmitters, hormones, sensory stimuli (touch, pressure, light, sound, temperature).

What determines the amplitude and direction of a graded potential?

Amplitude = stimulus strength; direction = ion movement (depolarizing or hyperpolarizing).

What is decremental conduction?

Graded potentials decay with distance from the stimulus site.

What is threshold?

The depolarized Vm at which voltage-gated channels open, triggering an action potential.

How is threshold reached?

Via ligand-gated channel opening or local current flow from an adjacent AP.

What are the key properties of action potentials?

All-or-none, always same amplitude, do not decay, propagate along excitable membranes.

What happens when voltage-gated Na+, K+, and Ca2+ channels open?

Na+: depolarization; K+: repolarization/hyperpolarization; Ca2+: depolarization.

How do Na+ and K+ channels differ in kinetics?

Both open with depolarization; Na+ channels open quickly, K+ channels open more slowly.

What are the transition states of a voltage-gated Na+ channel?

Resting (closed), activated (open), inactivated (blocked by inactivation gate until repolarization).

What are the phases of an action potential?

1) Resting Vm; 2) Threshold; 3) Rapid depolarization (Na+ influx); 4) Peak (Na+ inactivation, K+ opening); 5) Repolarization (K+ efflux); 6) Hyperpolarization; 7) Return to resting Vm.

What changes in permeability occur during an AP?

Large increase in Na+ permeability during depolarization, followed by increased K+ permeability during repolarization.

What is the refractory period?

Time after an AP when another AP cannot (absolute) or is harder (relative) to fire.

What is the absolute refractory period?

Na+ channels are inactivated → no new AP possible.

What is the relative refractory period?

Membrane is hyperpolarized → requires stronger stimulus to reach threshold.

Why do APs propagate in only one direction?

Refractory periods prevent reactivation of previously depolarized regions.

How do graded potentials differ from action potentials?

Graded: depolarizing/hyperpolarizing, proportional to stimulus, local/decremental.

APs: only depolarizing, all-or-none, uniform amplitude, propagate without decay.

What factors affect speed of AP propagation?

Axon diameter (larger = faster), myelination (insulation prevents charge leak, enables saltatory conduction), channel density.

What is decremental conduction?

The property of graded potentials where the change in membrane potential diminishes with distance from the site of stimulation, because charge dissipates along the membrane.

What is saltatory conduction?

APs “jump” between nodes of Ranvier in myelinated axons, increasing conduction speed.

What are the nodes of ranvier?

The spaces in between myelin sheaths that have a very high density of V-gated Na+ channels.

Describe how intracellular fluid relates to signal propagation in neurons.

Intracellular fluid is a highly conductive electrolyte solution. This causes decremental conduction along the membrane.

Compare conduction speed: myelinated vs unmyelinated.

Unmyelinated: ~0.5 m/s; Myelinated: ~100 m/s (head-to-toe in 0.02 s vs 4 s).

What are peripheral nerve fiber types and their conduction speeds?

• Aα: Somatomotor/proprioception; 12–20 μm, myelinated, 80–120 m/s

• Aβ: Touch/pressure; 5–12 μm, myelinated, 35–75 m/s

• Aγ: Muscle spindle motor; 3–6 μm, myelinated, 12–30 m/s

• Aδ: Acute pain/temp, fine touch; 2–5 μm, myelinated, 5–30 m/s

• B: Preganglionic autonomic; <3 μm, myelinated, 3–15 m/s

• C: Aching pain, touch, postganglionic autonomic; 0.3–1.3 μm, unmyelinated, 0.5–2.5 m/s

What happens in demyelination?

Reduced conduction speed, reduced spiking frequency, possible conduction block, and ectopic activation (neighboring neurons activated).

What diseases involve demyelination?

Multiple sclerosis (CNS, autoimmune, poor recovery) and Guillain-Barré (PNS, often post-viral, recovery possible with remyelination).

Does an AP significantly alter ion concentrations?

No, only ~0.06% of intracellular Na+ is moved; bulk ion concentrations remain unchanged.

What happens if voltage-gated Na+ channels are blocked (e.g., tetrodotoxin)?

Loss of AP propagation → numbness, paralysis, respiratory failure.

What happens if voltage-gated Na+ channels are prevented from closing?

No APs (stuck in absolute refractory period) → mechanism of local anesthetics.

How do local anesthetics (LAs) work?

Bind cytoplasmic side of Na+ channels, stabilize inactivated state, prevent reopening.

Which form of a local anesthetic crosses membranes?

Free base (non-ionized).

Which form of a local anesthetic is active at the channel?

Ionized form.

How does pH affect local anesthetic effectiveness?

• Lower pH (acidic): more ionized, less able to cross membrane → less effective.

• Higher pH (basic): more free base, better penetration.

• Infected/inflamed tissue is acidic, reducing LA effectiveness.