Source: UF APK2105 Elite Workbook v2 (Final Edition), Chapters 7 + 8 + 12
Tags: action potential, resting membrane potential, ion channels, voltage-gated sodium channels, potassium leak channels, depolarization, repolarization, hyperpolarization, threshold, all-or-none, graded potential, EPSP, IPSP, spatial summation, temporal summation, refractory period, conduction velocity, myelination, saltatory conduction, Schwann cells, axon hillock, Na/K ATPase, Nernst equation, neurophysiology, UF APK2105
Difficulty: Intermediate | Prerequisites: Basic cell biology, membrane structure, diffusion and osmosis.
This topic is the electrical foundation of the entire nervous system. Every sensation you feel, every movement you make, and every thought you have depends on neurons generating and transmitting electrical signals. Before tackling the neuromuscular junction or muscle contraction (Chapters 8 and 12), you need a solid grasp of how neurons create a resting membrane potential, how they fire action potentials, how those signals travel along an axon, and how neurons integrate information from multiple inputs. If membrane potentials do not make sense, everything downstream will feel arbitrary.
Neurons maintain a negative resting membrane potential mainly through K+ leak channels. When threshold is reached, voltage-gated Na+ channels open to produce an all-or-none action potential whose amplitude never changes, but whose frequency encodes stimulus strength. Myelination and axon diameter control how fast signals travel, while spatial and temporal summation determine whether a neuron fires at all.
Resting membrane potential (RMP)
The voltage difference across a neuron's membrane at rest, typically around -70 mV. It exists primarily because K+ leak channels allow potassium to flow out, leaving the inside more negative.
In simple terms, think of it as the neuron's "standby voltage," the baseline it returns to between signals.
Voltage-gated Na+ channels
Membrane proteins that open in response to depolarization, allowing Na+ to rush into the cell and drive the membrane toward +30 mV. They have two gates: an activation gate (opens quickly) and an inactivation gate (closes with a slight delay), which is why they self-limit.
In simple terms, these are the channels responsible for the rapid upstroke of the action potential.
Voltage-gated K+ channels
Membrane proteins that open more slowly than Na+ channels during an action potential, allowing K+ to leave the cell and restore the negative membrane potential (repolarization). Because they close slowly, they can overshoot the resting level, producing a brief hyperpolarization.
In simple terms, these channels bring the neuron back down after it fires.
K+ leak channels
Channels that are open at rest, allowing K+ to passively diffuse out of the cell. They are the main contributors to the resting membrane potential.
In simple terms, they are the reason the inside of a resting neuron is negative.
Threshold
The membrane voltage (roughly -55 mV) at which enough voltage-gated Na+ channels open to trigger the positive-feedback loop that produces a full action potential.
In simple terms, this is the "tipping point." Below it, nothing fires. At or above it, a full action potential is guaranteed.
All-or-none principle
Once threshold is reached, an action potential fires at full amplitude regardless of how strong the stimulus is. A stronger stimulus increases firing frequency, not the size of each action potential.
In simple terms, action potentials are like light switches: they are either fully on or fully off.
Depolarization
A shift in membrane potential toward a less negative (or positive) value. During an action potential, this is driven by Na+ influx.
Repolarization
The return of membrane potential toward its resting value, driven primarily by K+ efflux through voltage-gated K+ channels and Na+ channel inactivation.
Hyperpolarization (undershoot)
A brief dip below the resting membrane potential at the end of an action potential, caused by the slow closure of voltage-gated K+ channels.
Absolute refractory period
The interval during which no stimulus, regardless of strength, can trigger a second action potential. This is because voltage-gated Na+ channels are inactivated and cannot reopen until they reset.
Relative refractory period
The interval immediately after the absolute refractory period during which a stronger-than-normal stimulus can trigger an action potential. The main contributor is the continued opening of voltage-gated K+ channels, which opposes depolarization.
Graded potential
A local, variable-amplitude change in membrane potential that decreases with distance from the stimulus. Graded potentials can summate (add together), unlike action potentials.
In simple terms, these are small, local voltage changes that "vote" on whether the neuron fires.
EPSP (excitatory postsynaptic potential)
A graded depolarization of the postsynaptic membrane, typically produced by Na+ influx through ligand-gated channels. Moves the membrane closer to threshold.
IPSP (inhibitory postsynaptic potential)
A graded hyperpolarization of the postsynaptic membrane, typically produced by Cl- influx (e.g. through GABA_A receptors) or K+ efflux. Moves the membrane away from threshold.
Spatial summation
The combination of graded potentials arriving simultaneously from multiple different presynaptic neurons at different synapses on the same postsynaptic cell.
Temporal summation
The combination of graded potentials arriving in rapid succession from the same presynaptic neuron before earlier signals have decayed.
Saltatory conduction
The rapid mode of action potential propagation in myelinated axons, where the signal "jumps" from one node of Ranvier to the next rather than travelling continuously along the membrane.
Myelination
The wrapping of an axon by Schwann cells (PNS) or oligodendrocytes (CNS). Myelin increases membrane resistance and decreases ion leakage, allowing local currents to spread farther before needing regeneration, which increases conduction velocity.
Node of Ranvier
A gap in the myelin sheath where voltage-gated Na+ channels are concentrated and the action potential is regenerated.
Na+/K+ ATPase (sodium-potassium pump)
An active transporter that moves 3 Na+ out and 2 K+ in per ATP consumed. It maintains the concentration gradients that underlie the resting membrane potential and runs continuously, even at rest.
Axon hillock (trigger zone)
The region of the neuron where EPSPs and IPSPs are integrated and where the action potential is initiated if the net depolarization reaches threshold.
Membrane resistance
A measure of how difficult it is for ions to cross the membrane. Higher resistance (fewer open channels, thicker myelin) means less current leaks out, so signals travel farther before decaying.
Pseudounipolar neuron
A neuron with a single process that splits into two branches. This is the structural type most commonly associated with general sensory neurons entering the spinal cord.
Kinesin
A motor protein that transports materials (including synaptic vesicles) along microtubules from the cell body toward the axon terminal (anterograde transport). Blocking kinesin starves the terminal of vesicles and other cargo.
The resting membrane potential is set mainly by K+ leak channels, which make the membrane far more permeable to K+ than to Na+ at rest.
If all K+ leak channels are blocked, the resting membrane potential becomes less negative (depolarises), because the dominant force holding it near the K+ equilibrium potential is removed (Q41: answer A).
The Na+/K+ ATPase consumes ATP continuously, even between action potentials, to maintain the Na+ and K+ concentration gradients (Q75: answer B).
Raising extracellular K+ reduces the K+ concentration gradient. Initially this depolarises the neuron slightly, moving it closer to threshold and making it easier to excite (Q18: answer B).
With further increases, the sustained depolarization inactivates voltage-gated Na+ channels (they enter a closed, inactivated state and cannot reopen). This makes action potentials difficult or impossible to generate (Q61: answer A).
If voltage-gated Na+ channels open normally but close much more slowly, Na+ continues to flow in for longer, producing a longer depolarization phase and delayed repolarization (Q1: answer B).
If voltage-gated K+ channels fail to open, repolarization is delayed because there is no outward K+ current to restore the negative membrane potential (Q59: answer A).
If voltage-gated Na+ channels fail to activate at threshold, no action potential is generated even though the resting membrane potential is normal (Q21: answer A).
Action potential amplitude remains constant regardless of stimulus strength. A stronger stimulus increases firing frequency, not amplitude (Q5: answer B).
The body grades the intensity of a stimulus by changing how often a neuron fires, not how large each action potential is.
The absolute refractory period is caused by Na+ channel inactivation: the channels physically cannot reopen.
The relative refractory period is caused primarily by continued opening of voltage-gated K+ channels, which creates an extra hyperpolarizing current that must be overcome (Q15: answer B).
At very high stimulation frequencies (e.g. 200 Hz), Na+ channels may not recover from inactivation fast enough, so action potentials become less frequent despite identical stimulation (Q24: answer B).
Only graded potentials can summate. Action potentials are all-or-none and do not add together (Q25: answer B).
Both require ion channels. Both change membrane voltage. Action potentials travel farther because they are regenerated; graded potentials decay with distance.
The axon hillock integrates all incoming EPSPs and IPSPs. If the net depolarization at the hillock reaches threshold, an action potential fires.
4 EPSPs minus 3 IPSPs can fail to reach threshold if the net depolarization is insufficient (Q10: answer B).
5 small EPSPs minus 1 large IPSP can still reach threshold if spatial and temporal integration favours excitation (Q45: answer A).
One large EPSP arriving twice in rapid succession (temporal summation) can overcome inhibition from four moderate IPSPs that were present with only a single EPSP (Q68: answer B).
Spatial summation involves multiple neurons synapsing simultaneously on one postsynaptic cell (Q30: answer B).
If numerous EPSPs arrive simultaneously yet no action potential occurs, a likely explanation is an abnormally high Na+ channel threshold (Q71: answer A).
Blocking ligand-gated Na+ channels on the postsynaptic membrane directly reduces the EPSP because fewer ions enter the cell in response to neurotransmitter binding (Q13: answer A).
Slower neurotransmitter removal from the synaptic cleft prolongs the EPSP duration because the neurotransmitter keeps activating receptors for longer (Q56: answer B).
Increasing the threshold for opening voltage-gated Na+ channels means a larger depolarization is needed to fire, reducing AP frequency while the resting potential stays the same (Q46: answer A).
Two factors increase conduction velocity: larger axon diameter (lower internal resistance) and myelination (higher membrane resistance, enabling saltatory conduction).
Myelination increases conduction velocity because current spreads farther beneath the myelin before needing to be regenerated at the next node of Ranvier (Q44: answer B).
Increasing myelination increases conduction velocity without changing action potential amplitude, since amplitude is determined by ion channel properties and concentrations, not by how far local currents travel (Q11: answer A).
Comparing a large-diameter unmyelinated neuron (A) with a small-diameter myelinated neuron (B): you cannot determine which is faster without more specific data, because both diameter and myelination contribute (Q63: answer D).
Schwann cells form the myelin sheath in the PNS. When they degenerate, saltatory conduction is lost and conduction velocity drops dramatically.
Action potential generation at the axon hillock is most preserved because the hillock does not depend on myelin (Q4: answer C).
Opening additional K+ leak channels most decreases membrane resistance because there are more open pathways for ions to cross (Q23: answer A).
General sensory neurons entering the spinal cord are most commonly pseudounipolar (Q27: answer C).
Kinesin moves materials toward the axon terminal (anterograde transport). A toxin blocking kinesin most affects synaptic vesicles moving toward the terminal (Q26: answer A).
Ion movements through channels (Na+ entry, Ca2+ release from SR) and ATP synthesis inside mitochondria are not dependent on kinesin-based transport.
Students often think a stronger stimulus produces a bigger action potential. It does not. Amplitude is fixed; only frequency changes.
Students confuse the absolute and relative refractory periods. The absolute period is about Na+ channel inactivation (nothing can fire). The relative period is about lingering K+ channel opening (harder to fire, but possible with a strong stimulus).
Students sometimes assume blocking K+ leak channels would hyperpolarise the cell. The opposite is true: removing the main source of the resting potential's negativity makes the membrane less negative.
Students often think myelination changes the size of the action potential. It changes the speed of propagation, not the amplitude.
⚠️ The all-or-none principle and frequency coding are tested heavily. Know that amplitude is constant, frequency encodes strength.
⚠️ Be able to distinguish absolute vs. relative refractory periods by mechanism (Na+ inactivation vs. lingering K+ conductance).
⚠️ Hyperkalemia questions often have two stages: initial excitability increase, then Na+ channel inactivation and inability to fire. Know both phases.
⚠️ Conduction velocity questions test whether you can identify the role of myelination (membrane resistance, saltatory conduction) separately from axon diameter.
⚠️ Summation questions require you to reason about net depolarization at the axon hillock, not just count EPSPs vs. IPSPs.
True or False: A stronger stimulus produces a larger action potential.
Fill in the blank: The resting membrane potential is primarily set by ______ leak channels.
True or False: During the relative refractory period, it is impossible to generate an action potential regardless of stimulus strength.
Fill in the blank: Myelination increases conduction velocity by allowing local currents to spread ______ before regeneration at nodes of Ranvier.
True or False: Spatial summation involves one presynaptic neuron firing repeatedly.
Answers: 1. False (amplitude is constant). 2. K+ (potassium). 3. False (that describes the absolute refractory period; during the relative period, a stronger stimulus can fire an AP). 4. farther. 5. False (that is temporal summation; spatial summation involves multiple neurons firing simultaneously).
Q: A neuron's voltage-gated Na+ channels open normally but close much more slowly than usual. What is the most likely change to the action potential?
A: The depolarization phase is prolonged and repolarization is delayed, because Na+ continues to flow inward for a longer period.
Q: All K+ leak channels on a neuron are experimentally blocked. What happens to the resting membrane potential?
A: It becomes less negative (depolarises), because K+ leak channels are the primary source of the resting potential's negativity.
Q: Why does action potential amplitude remain constant when stimulus intensity increases?
A: Because action potentials are all-or-none events. Once threshold is reached, the same complement of voltage-gated Na+ channels opens fully, producing the same amplitude regardless of how strong the original stimulus was.
Q: A neuron is stimulated at 200 Hz and eventually fires less frequently despite identical stimulation. What is the most likely mechanism?
A: Na+ channels fail to recover from inactivation rapidly enough between stimuli, so some stimuli arrive while channels are still inactivated and cannot reopen.
Q: Which event contributes most to the relative refractory period?
A: Continued opening of voltage-gated K+ channels, which produces an outward current opposing depolarization and requiring a stronger-than-normal stimulus to reach threshold.
Q: A neuron receives 4 EPSPs and 3 IPSPs simultaneously, and threshold is not reached. What is the best explanation?
A: The net membrane depolarization (sum of all excitatory and inhibitory inputs) remained below threshold. The IPSPs counteracted enough of the excitatory input to prevent firing.
Q: Extracellular K+ concentration is raised substantially. Initially the neuron fires more easily, but eventually it stops generating action potentials. Why?
A: The persistent depolarization from elevated extracellular K+ holds voltage-gated Na+ channels in their inactivated state. They cannot reset to the closed (resting) state needed to open again, so action potentials cannot be generated.
Q: Which neuron type is most commonly associated with general sensory neurons entering the spinal cord?
A: Pseudounipolar neurons.
Q: A toxin blocks kinesin-mediated axonal transport. Which material is most affected?
A: Synaptic vesicles moving toward the axon terminal, because kinesin is the motor protein responsible for anterograde transport along microtubules.
This material connects directly to synaptic transmission and the neuromuscular junction (next set of notes), where presynaptic Ca2+ influx triggers vesicle release, and to muscle physiology, where the muscle action potential initiates excitation-contraction coupling. Understanding how ion channels set the resting potential and generate action potentials is also essential for cardiac physiology (Chapter 12 content on cardiac muscle refractory periods).
action potential, resting membrane potential, voltage-gated sodium channel, voltage-gated potassium channel, potassium leak channel, depolarization, repolarization, hyperpolarization, threshold, all-or-none law, graded potential, EPSP, IPSP, spatial summation, temporal summation, absolute refractory period, relative refractory period, saltatory conduction, myelination, Schwann cell, oligodendrocyte, node of Ranvier, axon hillock, trigger zone, Na/K ATPase, sodium-potassium pump, membrane resistance, conduction velocity, hyperkalemia, pseudounipolar, kinesin, axonal transport, APK2105, UF anatomy and physiology