Core mental model
Action potentials are predictable consequences of ion gradients and voltage-gated channels.
When membrane permeability to an ion increases, the membrane potential moves toward that ion's equilibrium potential.
Four-question method
Which channel opened?
Which ion moved?
Which direction?
Toward which equilibrium potential?
Signal transformation
Local graded input -> threshold -> regenerative Na+ opening -> spike propagation -> refractory reset
-70
mV neuron rest
-55
mV threshold
+60
mV ENa
-90
mV EK
Na+
High outside
Opening Na+ channels drives Na+ inward and pulls Vm toward +60 mV.
K+
High inside
Opening K+ channels drives K+ outward and pulls Vm toward -90 mV.
Ca2+
High outside
Opening Ca2+ channels depolarizes cells and can trigger contraction or transmitter release.
Neuron action potential
Phase map
threshold converts graded input into spike
Rest
K+ leak dominates. Voltage-gated Na+ channels are closed but available.
Threshold
Enough voltage-gated Na+ channels open to start regenerative depolarization.
Upstroke
Na+ influx creates positive feedback and a steep depolarizing spike.
Repolarize
Na+ channels inactivate while delayed K+ channels open.
AHP
K+ channels close slowly, so Vm moves closer to EK.
Na+ channel states
Closed but available
Resting membrane. Can open if threshold is reached.
Open
Rapid depolarization. Na+ enters down both chemical and electrical gradients.
Inactivated
Cannot reopen until repolarization restores availability.
Refractory logic
Absolute
no second AP possible
Voltage-gated Na+ channels are inactivated.
Relative
stronger stimulus needed
K+ conductance remains high and the membrane is hyperpolarized.
Signal types
Graded potential vs action potential
input decision vs long-distance signal
Graded
Variable size, can depolarize or hyperpolarize, decays with distance, can summate, and decides whether threshold is reached.
Action potential
All-or-none, stereotyped amplitude, regenerates along membrane, does not decay with distance, and cannot summate like graded inputs.
Conduction map
Diameter
Larger axons conduct faster because internal resistance is lower.
Myelin
Increases membrane resistance and decreases capacitance.
Nodes
Voltage-gated Na+ channels concentrate at nodes of Ranvier.
Saltatory
APs jump node to node: faster and more energy-efficient.
Direction of propagation
Forward because the membrane behind is refractory.
Local current depolarizes the next segment to threshold, while the previous segment has inactivated Na+ channels and cannot immediately fire again.
Frequency coding
Stronger stimulus means more spikes, not bigger spikes.
Action potentials are all-or-none. Stimulus intensity is encoded mainly by firing frequency.
Neuromuscular junction connection
Motor neuron AP -> presynaptic Ca2+ influx -> ACh release -> nicotinic receptor activation -> end-plate potential -> muscle AP -> T-tubules -> SR Ca2+ release -> contraction
End-plate potential
Graded potential at the NMJ.
Muscle AP
All-or-none Na+ upstroke across sarcolemma and T-tubules.
Ca2+ release
DHP receptors trigger ryanodine receptors; Ca2+ binds troponin C.
Excitable cell comparison
Neuron
Fast Na+ upstroke, short AP, no plateau, rapid signaling.
Skeletal muscle
Fast Na+ AP triggers SR Ca2+ release and contraction.
Ventricular cell
Phase 0 Na+, phase 2 Ca2+ plateau, long refractory period.
SA node
No stable rest. Phase 4 pacemaker drift, phase 0 Ca2+.
Ventricular myocyte phases
Phase 0: fast Na+ influx.
Phase 1: transient K+ efflux.
Phase 2: L-type Ca2+ influx balanced by K+ efflux creates the plateau.
Phase 3: K+ efflux repolarizes.
Phase 4: stable resting potential.
SA node pacemaker
Phase 4: spontaneous depolarization from funny current, T-type Ca2+ and autonomic tone.
Phase 0: L-type Ca2+ influx, not fast Na+.
Phase 3: K+ efflux repolarizes.
Sympathetic: steeper phase 4, threshold sooner.
Parasympathetic: flatter phase 4, more negative maximum diastolic potential.
Potassium and excitability
Hyperkalemia
Extracellular K+ rises, the K+ gradient falls, resting Vm becomes less negative. Severe depolarization can inactivate Na+ channels and slow conduction.
ECG: peaked T waves, PR prolongation, QRS widening, sine-wave pattern.
Hypokalemia
Extracellular K+ falls, the K+ gradient rises, resting Vm becomes more negative. Repolarization changes can promote arrhythmias.
ECG: ST depression, flattened T waves, prominent U waves.
Clinical hooks and blockers
Local anesthetics
Block voltage-gated Na+ channels, especially open/inactivated states.
TTX / saxitoxin
Block voltage-gated Na+ channels and prevent electrical conduction.
Botulinum
Blocks ACh release by SNARE cleavage; not the AP itself.
Demyelination
MS affects CNS myelin; GBS affects peripheral myelin.
Myasthenia
Postsynaptic nicotinic ACh receptor antibodies reduce end-plate potential.
Lambert-Eaton
Presynaptic voltage-gated Ca2+ channel antibodies reduce ACh release.
Hyperkalemia
Depolarizes rest and can inactivate Na+ channels.
Cardiac plateau
Long refractory period prevents tetany and preserves filling.
Final synthesis
To decode any spike
Name the channel, ion, direction of movement and equilibrium potential. The membrane follows the permeability.
To decode any disease
Ask whether the problem blocks channels, changes gradients, damages myelin, disrupts transmitter release, or changes cardiac refractory timing.