Action Potentials &
Synaptic Transmission
Master how neurons generate electrical signals and communicate across synapses: from resting potential to neurotransmitter release.
MCAT Biological Foundations
The Resting Membrane Potential
At rest, a neuron maintains a voltage difference across its membrane of approximately \(-70\,\text{mV}\). The inside is negative relative to the outside. This is the resting membrane potential.
\(\text{Na}^+\)/\(\text{K}^+\) ATPase
Pumps 3 \(\text{Na}^+\) out and 2 \(\text{K}^+\) in per ATP hydrolyzed, creating a net negative interior.
\(\text{K}^+\) Leak Channels
\(\text{K}^+\) diffuses out through leak channels down its concentration gradient, making the interior more negative.
Ion Distributions Across the Membrane
Why Action Potentials Matter
Action potentials are the fundamental electrical signals of the nervous system. Every sensation, thought, and motor command depends on neurons firing action potentials and transmitting signals across synapses.
Speed
Signals travel up to 120 m/s in myelinated neurons, enabling rapid reflexes.
All-or-None
Once threshold is reached, the action potential fires fully: no partial signals.
Integration
Synaptic transmission allows neurons to sum excitatory and inhibitory inputs.
Phases of the Action Potential
Depolarization: Opening \(\text{Na}^+\) Gates
1
Stimulus received: a graded potential (e.g., EPSP) depolarizes the membrane toward threshold at \(-55\,\text{mV}\).
2
Voltage-gated \(\text{Na}^+\) channels open: \(\text{Na}^+\) rushes in down its electrochemical gradient, rapidly making the interior more positive.
3
Positive feedback loop: More \(\text{Na}^+\) entry causes more depolarization, opening more \(\text{Na}^+\) channels (Hodgkin cycle).
4
Peak: Membrane potential reaches approximately \(+40\,\text{mV}\), approaching \(E_{\text{Na}} \approx +60\,\text{mV}\).
Repolarization & Refractory Periods
After the peak, voltage-gated \(\text{Na}^+\) channels enter an inactivated state (ball-and-chain mechanism), and voltage-gated \(\text{K}^+\) channels finally open, allowing \(\text{K}^+\) to flow out and restore negative interior charge.
Absolute Refractory
\(\text{Na}^+\) channels are inactivated: no stimulus of any strength can trigger another action potential.
Relative Refractory
Some \(\text{Na}^+\) channels have reset, but the membrane is hyperpolarized. A stronger-than-normal stimulus is needed.
Graded vs. Action Potentials
| Graded Potential | Action Potential | |
|---|---|---|
| Amplitude | Variable (proportional to stimulus) | All-or-none (fixed amplitude) |
| Direction | Decremental (fades with distance) | Non-decremental (self-propagating) |
| Summation | Temporal and spatial summation | No summation (refractory period) |
| Location | Dendrites, cell body | Axon hillock to axon terminal |
| Channels | Ligand-gated or mechanically gated | Voltage-gated \(\text{Na}^+\) and \(\text{K}^+\) |
Saltatory Conduction & Myelin
The Chemical Synapse
Steps of Synaptic Transmission
1
Action potential arrives at the axon terminal (presynaptic neuron).
2
Voltage-gated \(\text{Ca}^{2+}\) channels open: \(\text{Ca}^{2+}\) flows into the presynaptic terminal.
3
Vesicle exocytosis: \(\text{Ca}^{2+}\) triggers synaptic vesicles to fuse with the membrane and release neurotransmitters into the synaptic cleft.
4
Receptor binding: neurotransmitters bind to ligand-gated ion channels (ionotropic) or G protein-coupled receptors (metabotropic) on the postsynaptic cell.
5
Postsynaptic response: Ion channels open, producing an EPSP (excitatory) or IPSP (inhibitory).
6
Signal termination: neurotransmitters are removed by reuptake, enzymatic degradation, or diffusion.
EPSPs vs. IPSPs
EPSP (Excitatory)
Depolarizes the postsynaptic membrane. Driven by \(\text{Na}^+\) influx (or mixed cation channels). Moves membrane potential toward threshold.
IPSP (Inhibitory)
Hyperpolarizes the postsynaptic membrane. Driven by \(\text{Cl}^-\) influx or \(\text{K}^+\) efflux. Moves membrane potential away from threshold.
Key Neurotransmitters
| Neurotransmitter | Type | Key Function |
|---|---|---|
| Acetylcholine (ACh) | Excitatory/Inhibitory | NMJ contraction, parasympathetic |
| Glutamate | Excitatory | Main excitatory NT in CNS |
| GABA | Inhibitory | Main inhibitory NT in CNS |
| Norepinephrine | Excitatory | Sympathetic "fight or flight" |
| Dopamine | Excitatory/Modulatory | Reward, motor control |
| Serotonin | Modulatory | Mood, sleep, appetite |
How to Solve AP/Synapse Problems
1
Identify the phase: Is the question about resting potential, depolarization, repolarization, or synaptic transmission?
2
Determine the ion: Which ion is moving (\(\text{Na}^+\), \(\text{K}^+\), \(\text{Ca}^{2+}\), \(\text{Cl}^-\))? In which direction?
3
Apply the electrochemical gradient: Ions move from high to low concentration, but also toward opposite charge. Use the Nernst equation if quantitative.
4
Check the channel type: Voltage-gated, ligand-gated, or leak? This tells you the trigger mechanism.
5
Predict the outcome: Will the membrane depolarize or hyperpolarize? Will the signal be excitatory or inhibitory?
Example: Tetrodotoxin (TTX)
Scenario: Tetrodotoxin (from puffer fish) blocks voltage-gated \(\text{Na}^+\) channels. What happens to neural signaling?
1
Identify the target: Voltage-gated \(\text{Na}^+\) channels on the axon.
2
Effect of blockade: \(\text{Na}^+\) cannot enter during depolarization, so the membrane cannot reach threshold.
3
Result: No action potentials can be generated. The neuron cannot fire.
4
Clinical outcome: Paralysis and potentially death, because motor neurons cannot signal muscles to contract (including the diaphragm).
Example: Nerve Gas & ACh
Scenario: An organophosphate nerve agent inhibits acetylcholinesterase (AChE), the enzyme that degrades acetylcholine in the synaptic cleft. What is the physiological effect?
1
Normal process: ACh is released, binds receptors, then AChE rapidly breaks it down to stop the signal.
2
With AChE inhibited: ACh accumulates in the synaptic cleft and continuously stimulates postsynaptic receptors.
3
At the NMJ: Sustained muscle contraction (spasm), followed by desensitization and eventual paralysis.
4
Autonomic effects: Excessive parasympathetic stimulation: salivation, lacrimation, urination, defecation (SLUD).
Example: Nernst Equation Calculation
Problem: Calculate the equilibrium potential for \(\text{Na}^+\) at 37°C given \([\text{Na}^+]_{\text{out}} = 145\,\text{mM}\) and \([\text{Na}^+]_{\text{in}} = 15\,\text{mM}\).
1
Plug in values: \( E_{\text{Na}} = \frac{61.5}{+1} \cdot \log_{10}\frac{145}{15} \)
2
Compute ratio: \( \frac{145}{15} \approx 9.67 \)
3
Take log: \( \log_{10}(9.67) \approx 0.986 \)
4
Final answer: \( E_{\text{Na}} \approx 61.5 \times 0.986 \approx \) \(+60.6\,\text{mV}\)
Common Mistakes
✕ Confusing Inactivated vs. Closed
Closed \(\text{Na}^+\) channels can be opened by depolarization. Inactivated channels cannot: they must first return to the closed state. This distinction defines the absolute refractory period.
✕ "More \(\text{Na}^+\)/\(\text{K}^+\) pump = AP"
The pump maintains resting potential but does not directly produce the action potential. The AP is driven by passive ion flow through voltage-gated channels.
✕ \(\text{Ca}^{2+}\) Enters Postsynaptically
At a chemical synapse, \(\text{Ca}^{2+}\) enters the presynaptic terminal to trigger vesicle fusion. The postsynaptic response involves \(\text{Na}^+\), \(\text{K}^+\), or \(\text{Cl}^-\), not \(\text{Ca}^{2+}\) (in most cases).
Summary: Action Potential Phases
| Phase | Ion Movement | Voltage Change | Channel State |
|---|---|---|---|
| Resting | \(\text{K}^+\) leak out | \(-70\,\text{mV}\) (stable) | \(\text{Na}^+\) closed, \(\text{K}^+\) leak open |
| Depolarization | \(\text{Na}^+\) rushes in | \(-70 \to +40\,\text{mV}\) | \(\text{Na}^+\) open, \(\text{K}^+\) closed |
| Repolarization | \(\text{K}^+\) flows out | \(+40 \to -70\,\text{mV}\) | \(\text{Na}^+\) inactivated, \(\text{K}^+\) open |
| Hyperpolarization | \(\text{K}^+\) still flowing out | Undershoot to \(-90\,\text{mV}\) | \(\text{Na}^+\) resetting, \(\text{K}^+\) slowly closing |
| Return to Rest | Pump restores gradients | Back to \(-70\,\text{mV}\) | All channels reset |
Question 1 of 5
During the absolute refractory period, why can't a second action potential be initiated regardless of stimulus strength?
During the absolute refractory period, the voltage-gated \(\text{Na}^+\) channels have entered an inactivated conformation (the inactivation gate has closed). They physically cannot open until the membrane repolarizes and the channel resets to the closed (but activatable) state. This is distinct from simply being "closed."
Question 2 of 5
A neuron receives 3 simultaneous EPSPs from different presynaptic neurons. The combined depolarization reaches \(-55\,\text{mV}\) at the axon hillock. This is an example of:
Spatial summation occurs when multiple presynaptic neurons fire simultaneously and their individual EPSPs combine at the axon hillock. Temporal summation, by contrast, involves rapid successive signals from a single presynaptic neuron.
Question 3 of 5
A drug blocks voltage-gated \(\text{Ca}^{2+}\) channels on presynaptic terminals. What is the most direct consequence?
\(\text{Ca}^{2+}\) influx into the presynaptic terminal is the trigger for vesicle fusion with the presynaptic membrane (exocytosis). Without \(\text{Ca}^{2+}\) entry, vesicles remain docked but cannot release their neurotransmitter contents into the synaptic cleft.
Question 4 of 5
Demyelinating diseases like multiple sclerosis impair neural signaling primarily because:
Myelin enables saltatory conduction, where the action potential jumps between Nodes of Ranvier. When myelin is damaged, the signal must travel continuously along the axon membrane, which is much slower and may fail entirely due to current dissipation.
Question 5 of 5
If the extracellular concentration of \(\text{K}^+\) is experimentally increased from 5 mM to 50 mM, what happens to the resting membrane potential?
By the Nernst equation, \( E_K = \frac{61.5}{+1}\log\frac{[\text{K}^+]_{\text{out}}}{[\text{K}^+]_{\text{in}}} \). Increasing extracellular \(\text{K}^+\) decreases the concentration gradient, so \(E_K\) becomes less negative. Since the resting potential is largely determined by \(\text{K}^+\) permeability, the membrane depolarizes. This is why hyperkalemia is clinically dangerous.