Difficulty: Intermediate | Prerequisites: Nervous system divisions, basic ion chemistry (Na⁺, K⁺, Ca²⁺, Cl⁻), neuroglia and myelination.
Tags: resting membrane potential, action potential, depolarisation, repolarisation, hyperpolarisation, threshold, sodium-potassium pump, Na⁺/K⁺-ATPase, voltage-gated channels, all-or-none, synapse, synaptic transmission, neurotransmitter, synaptic cleft, excitatory, inhibitory, EPSP, IPSP, calcium, vesicles
Neurons communicate using electrical signals that travel along their membranes and chemical signals that cross the gaps between them. This topic covers the three core mechanisms: how a neuron maintains its electrical "ready state" (resting membrane potential), how it fires a signal (action potential), and how that signal passes to the next cell (synaptic transmission).
If you are not comfortable with the basic ion species (Na⁺, K⁺, Ca²⁺) and the concept of concentration gradients, review those first. You should also know the difference between CNS and PNS glia, particularly myelinating cells, since myelination directly affects how fast these signals travel.
This is the electrical and chemical heart of neuroscience. Every later topic, from reflexes to brain function to pharmacology, relies on your understanding of how neurons generate and transmit signals.
A neuron at rest sits at about −70 mV, maintained by the sodium-potassium pump and selective membrane permeability to K⁺. When a stimulus reaches threshold (about −55 mV), voltage-gated Na⁺ channels open and the cell fires an all-or-none action potential that travels along the axon. At the synapse, the arriving signal triggers Ca²⁺ influx, neurotransmitter release, and a response in the next cell.
Resting membrane potential
The voltage difference across a neuron's membrane when it is not sending a signal, typically around −70 mV (inside negative relative to outside). Think of it as a loaded spring: the cell is primed and ready to fire.
Sodium-potassium pump (Na⁺/K⁺-ATPase)
An active transport protein that moves 3 Na⁺ ions out of the cell and 2 K⁺ ions in per cycle, using one ATP. This creates and maintains the concentration gradients that underpin the resting potential.
Selective permeability
The membrane's tendency to allow some ions through more readily than others. At rest, the membrane is far more permeable to K⁺ than to Na⁺, so K⁺ leaks out, leaving the inside more negative.
Electrochemical equilibrium
The point where the electrical gradient pulling an ion one way exactly balances the concentration gradient pushing it the other way. For K⁺, this is near −90 mV; the resting potential of −70 mV reflects the slight Na⁺ leak inward as well.
Threshold
The membrane voltage (roughly −55 mV) at which voltage-gated Na⁺ channels open in sufficient numbers to trigger a self-reinforcing depolarisation. Below threshold, no action potential. At or above it, the cell fires fully.
Depolarisation
A shift in membrane potential toward zero (and beyond, to about +30 mV) caused by Na⁺ rushing into the cell through voltage-gated channels.
Repolarisation
The return toward resting potential. Na⁺ channels inactivate and voltage-gated K⁺ channels open, allowing K⁺ to flow out of the cell and restore the negative internal charge.
Hyperpolarisation (undershoot)
A brief dip below resting potential (more negative than −70 mV) that occurs because K⁺ channels stay open slightly longer than needed. The membrane then stabilises back to −70 mV.
All-or-none principle
An action potential either fires at full amplitude or does not fire at all. There is no partial action potential. Signal strength is encoded by the frequency of action potentials, not their size.
Refractory period
The brief interval after an action potential during which the neuron cannot fire again (absolute refractory period) or requires a stronger-than-normal stimulus to fire (relative refractory period). This ensures one-directional propagation along the axon.
Synapse
The junction where a signal passes from one neuron (presynaptic) to another cell (postsynaptic), which may be another neuron, a muscle cell, or a gland cell.
Synaptic cleft
The narrow gap (about 20–40 nm) between the presynaptic and postsynaptic membranes. Neurotransmitters cross this gap.
Neurotransmitter
A chemical messenger released from synaptic vesicles into the cleft. Examples include acetylcholine, noradrenaline, dopamine, serotonin, GABA, and glutamate.
Excitatory postsynaptic potential (EPSP)
A small depolarisation of the postsynaptic membrane that makes the cell more likely to fire. In simple terms, an EPSP nudges the next cell closer to threshold.
Inhibitory postsynaptic potential (IPSP)
A small hyperpolarisation of the postsynaptic membrane that makes the cell less likely to fire. In simple terms, an IPSP pushes the next cell further from threshold.
The resting potential of approximately −70 mV depends on three things working together:
Na⁺/K⁺-ATPase pump – moves 3 Na⁺ out for every 2 K⁺ in, creating a net loss of positive charge from the cell with each cycle. This also sets up concentration gradients: high Na⁺ outside, high K⁺ inside.
Leak channels and selective permeability – the membrane has many more K⁺ leak channels than Na⁺ leak channels. K⁺ drifts outward down its concentration gradient, carrying positive charge out and leaving the interior negative.
Electrochemical equilibrium – K⁺ stops leaving when the electrical pull inward (the inside is increasingly negative) matches the concentration push outward. The resting potential is close to K⁺ equilibrium (−90 mV) but slightly less negative because a small amount of Na⁺ leaks in.
The resting potential matters because it is stored energy. The ion gradients are the neuron's battery, ready to be discharged the moment threshold is reached.
The action potential unfolds in three distinct phases:
Depolarisation – a stimulus (from a sensory receptor, another neuron, or an artificial electrode) pushes the membrane potential toward threshold (−55 mV). Once threshold is reached, voltage-gated Na⁺ channels open rapidly. Na⁺ floods in, driving the membrane potential to approximately +30 mV. This is a positive feedback loop: more depolarisation opens more Na⁺ channels.
Repolarisation – Na⁺ channels inactivate (they have a built-in timer). Voltage-gated K⁺ channels, which opened slightly later, are now fully open. K⁺ rushes out, restoring the negative interior.
Hyperpolarisation (undershoot) – K⁺ channels close slowly, so slightly too much K⁺ exits. The membrane briefly dips below −70 mV before the resting potential is re-established by the pump and leak channels.
Key points to lock in:
The all-or-none principle means there is no "half" action potential. Signal intensity is coded by firing frequency.
Action potentials propagate without losing strength (they are regenerated at each point along the axon).
Myelinated axons conduct faster because the action potential jumps between nodes of Ranvier (saltatory conduction), skipping the insulated segments.
The absolute refractory period prevents backward propagation: the region just behind the action potential cannot fire again immediately.
When an action potential reaches the axon terminal, the signal must cross to the next cell. The sequence:
Action potential arrives at the presynaptic terminal.
Voltage-gated Ca²⁺ channels open – calcium flows into the terminal.
Ca²⁺ triggers vesicle fusion – synaptic vesicles containing neurotransmitter move to the membrane and release their contents into the synaptic cleft by exocytosis.
Neurotransmitter binds receptors on the postsynaptic membrane, opening ligand-gated ion channels.
Postsynaptic response – depending on which ion channels open:
Na⁺ channels open → depolarisation → EPSP (excitatory)
Cl⁻ or K⁺ channels open → hyperpolarisation → IPSP (inhibitory)
Signal termination – neurotransmitter is removed from the cleft by one of three mechanisms:
Enzymatic breakdown (e.g. acetylcholinesterase breaks down acetylcholine)
Reuptake into the presynaptic neuron
Diffusion away from the cleft
The postsynaptic cell sums all incoming EPSPs and IPSPs. If the total depolarisation at the axon hillock reaches threshold, that cell fires its own action potential. This summation is how the nervous system integrates information from many sources simultaneously.
Nernst equation (conceptual)
For any single ion, the equilibrium potential can be calculated. You may not need to compute it at this level, but know that:
K⁺ equilibrium ≈ −90 mV
Na⁺ equilibrium ≈ +60 mV
The resting membrane potential (−70 mV) is a weighted average dominated by K⁺ permeability.
Action potential voltage timeline
Resting (−70 mV) → threshold (−55 mV) → peak depolarisation (+30 mV) → repolarisation → undershoot (below −70 mV) → return to rest (−70 mV).
Local anaesthetics (like lidocaine) work by blocking voltage-gated Na⁺ channels in peripheral nerves, preventing action potentials from reaching the brain as pain signals. Understanding the channel mechanism makes the pharmacology straightforward.
Many antidepressant and antianxiety medications target neurotransmitter reuptake at the synapse (e.g. SSRIs block serotonin reuptake), which is a direct application of the synaptic termination step.
Students frequently think a "stronger stimulus" produces a "bigger action potential." It does not. The action potential is all-or-none at a fixed amplitude. Stronger stimuli produce more frequent action potentials.
Mixing up which ion does what: Na⁺ rushes in during depolarisation, K⁺ rushes out during repolarisation. Not the other way round. Exam questions test this repeatedly.
Forgetting that Ca²⁺ is the trigger for neurotransmitter release at the synapse, not Na⁺ or K⁺. Calcium entry is the step that converts the electrical signal into a chemical one.
Assuming neurotransmitters are always excitatory. They can be inhibitory (e.g. GABA opens Cl⁻ channels, hyperpolarising the postsynaptic cell).
⚠️ Be able to draw and label an action potential graph: resting potential, threshold, depolarisation, repolarisation, hyperpolarisation, and the ions responsible at each stage.
⚠️ Understand the role of the Na⁺/K⁺ pump versus leak channels in maintaining resting potential. The pump is active transport (uses ATP); the leak channels are passive.
⚠️ Know the five steps of synaptic transmission in order, including the role of Ca²⁺. This is a standard sequence question.
⚠️ Be clear on the three ways neurotransmitter is removed from the cleft: enzymatic degradation, reuptake, diffusion.
True or false: The resting membrane potential is approximately +70 mV.
Fill in the blank: During depolarisation, voltage-gated _______ channels open first.
True or false: A stronger stimulus produces a larger action potential.
Fill in the blank: At the synapse, influx of _______ ions triggers vesicle fusion and neurotransmitter release.
True or false: An IPSP makes the postsynaptic neuron more likely to fire.
Answers: 1. False (−70 mV, inside negative). 2. Na⁺ (sodium). 3. False (all-or-none; stronger stimuli increase frequency, not amplitude). 4. Ca²⁺ (calcium). 5. False (IPSPs are inhibitory, making firing less likely).
Q: Describe the three factors that maintain the resting membrane potential.
A: (1) The Na⁺/K⁺-ATPase pump actively transports 3 Na⁺ out and 2 K⁺ in, creating concentration gradients. (2) Selective permeability, the membrane has more K⁺ leak channels, so K⁺ diffuses out, leaving the inside negative. (3) Electrochemical equilibrium, where the outward concentration gradient for K⁺ is balanced by the inward electrical gradient, stabilising the potential near −70 mV.
Q: Explain why action potentials propagate in one direction along an axon.
A: The absolute refractory period prevents the segment of membrane just behind the action potential from firing again immediately. Na⁺ channels in that region are inactivated and cannot reopen until they reset, so the action potential can only move forward into resting membrane.
Q: A drug blocks voltage-gated Ca²⁺ channels at the presynaptic terminal. What effect would this have on synaptic transmission?
A: Without Ca²⁺ entry, synaptic vesicles would not fuse with the presynaptic membrane. Neurotransmitter would not be released into the cleft, and the postsynaptic cell would receive no chemical signal. Synaptic transmission would be blocked.
Q: Distinguish between temporal summation and spatial summation at a synapse.
A: Temporal summation occurs when a single presynaptic neuron fires rapidly, stacking EPSPs before each one fades. Spatial summation occurs when multiple presynaptic neurons fire simultaneously, and their EPSPs combine at the postsynaptic cell. Both can bring the membrane to threshold.
This material links directly back to neuroglia: myelination by oligodendrocytes (CNS) and Schwann cells (PNS) enables saltatory conduction, which dramatically increases the speed of action potential propagation. It also connects forward to the autonomic nervous system, where the neurotransmitters at sympathetic and parasympathetic synapses (noradrenaline and acetylcholine, respectively) determine the organ-level effects you will study next.
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