Neurophysiology
Learning Objectives
By the end of this page, you should be able to:
- Explain how the resting membrane potential is generated and maintained
- Describe the sequence of events in an action potential, phase by phase
- Distinguish continuous conduction from saltatory conduction and explain why myelin speeds signal transmission
- Differentiate chemical and electrical synapses and describe the steps of chemical neurotransmission
- Identify the major neurotransmitters and their principal physiological roles
- Relate the organization of the CNS and PNS to how neural signals are processed and distributed
- Apply neurophysiological mechanisms to explain clinical phenomena (local anesthesia, demyelinating disease, neuromuscular blockade)
Quick Answer
Neurophysiology is the study of how neurons generate and transmit electrical and chemical signals to control every function in the body, from a knee-jerk reflex to conscious thought. The core idea is simple: neurons keep the inside of their membrane negatively charged relative to the outside (the resting membrane potential, about -70 mV) by controlling ion movement through channels and pumps. A strong enough stimulus flips this polarity for a split second — an action potential — that races down the axon and triggers neurotransmitter release at the synapse, passing the signal to the next cell. Nearly every drug that acts on the nervous system, and nearly every neurological disease, is best understood as a disruption of one step in this chain: the resting potential, the action potential, or synaptic transmission.
Neurons and Their Structure
A neuron is built to do one job extremely well: receive a signal at one end and deliver it, unchanged, to a very specific destination at the other end. Three structural regions make this possible.
- Dendrites — branching extensions that receive input from other neurons via synapses and convert it into small graded electrical changes.
- Cell body (soma) — contains the nucleus and organelles; integrates all the incoming graded signals arriving from the dendrites.
- Axon — a single long extension that carries the "decision" (an action potential) away from the soma toward the axon terminals, where neurotransmitter is released onto the next cell.
Functionally, neurons are classified by the direction of information they carry:
- Sensory (afferent) neurons carry information from receptors toward the CNS.
- Motor (efferent) neurons carry commands from the CNS to muscles and glands.
- Interneurons connect neurons within the CNS and account for the vast majority of neurons in the brain and spinal cord — they are where integration and decision-making happen.
The Resting Membrane Potential
Before a neuron can "fire," it needs a stable baseline to fire from. At rest, the inside of a neuron sits at about -70 mV relative to the outside. This voltage is not free — the cell spends ATP to create it, and two facts explain why it exists:
- Unequal ion distribution. The Na⁺/K⁺-ATPase pump continuously exports 3 Na⁺ ions for every 2 K⁺ ions it imports, keeping Na⁺ concentrated outside the cell and K⁺ concentrated inside.
- Selective permeability. At rest, the membrane has many more open K⁺ leak channels than Na⁺ channels, so K⁺ diffuses out down its concentration gradient far more easily than Na⁺ can diffuse in. This net loss of positive charge is what makes the inside negative.
The resting potential is close to, but not exactly at, the K⁺ equilibrium potential (~-90 mV) — the small amount of Na⁺ leaking in pulls it slightly less negative, to around -70 mV. This balance point is what every subsequent event in this chapter perturbs and restores.
Action Potentials
An action potential is an all-or-none electrical event that occurs when the membrane potential is pushed to a threshold (roughly -55 mV) by a strong enough depolarizing stimulus. Unlike graded potentials (which vary in size and decay with distance), an action potential is the same size every time it fires and travels without losing amplitude — this is what allows it to carry a signal reliably over long distances, like from your spinal cord to your big toe.
The phases, in order:
- Resting state — membrane at -70 mV; voltage-gated Na⁺ and K⁺ channels are closed.
- Depolarization — a stimulus brings the membrane to threshold; voltage-gated Na⁺ channels open, Na⁺ rushes in, and the membrane potential rapidly swings positive (toward +30 mV).
- Repolarization — Na⁺ channels inactivate (close and become temporarily unresponsive) while voltage-gated K⁺ channels open; K⁺ flows out, driving the membrane potential back down.
- Hyperpolarization (undershoot) — K⁺ channels close more slowly than they opened, so the membrane briefly dips below -70 mV before settling back to rest.
- Refractory periods — during the absolute refractory period (roughly corresponding to depolarization and most of repolarization), Na⁺ channels are inactivated and no stimulus, however strong, can trigger another action potential. During the relative refractory period (during hyperpolarization), only an unusually strong stimulus can trigger a new one. These refractory periods enforce one-way propagation and cap the maximum firing rate of a neuron.
Propagation: Continuous vs. Saltatory Conduction
Once triggered, an action potential must self-propagate down the entire length of the axon. In unmyelinated axons, this happens through continuous conduction: depolarization at one patch of membrane passively spreads to the adjacent patch, bringing it to threshold and regenerating the action potential step by step — relatively slow and metabolically expensive, since the whole membrane must be re-depolarized.
Myelinated axons use saltatory conduction. Schwann cells (PNS) or oligodendrocytes (CNS) wrap the axon in myelin, an insulating sheath interrupted at regular intervals by the nodes of Ranvier, where voltage-gated Na⁺ channels are concentrated. Because the myelinated segments cannot leak current, the depolarization jumps ("saltare" = to leap) from node to node instead of regenerating continuously. This dramatically increases conduction velocity — up to 120 m/s in large myelinated fibers versus about 1 m/s in unmyelinated fibers — while using far less ATP, since the pump only has to restore ion gradients at the nodes.
Synapses and Chemical Neurotransmission
A synapse is the junction where one neuron communicates with the next. There are two types:
- Electrical synapses connect two neurons directly through gap junctions, allowing ion current to flow instantly between cells. They are fast and bidirectional but offer little flexibility — useful where synchronized firing matters, such as in cardiac muscle or some brainstem circuits.
- Chemical synapses are far more common in the human nervous system and involve several discrete steps:
- An action potential arrives at the presynaptic axon terminal.
- Depolarization opens voltage-gated Ca²⁺ channels; Ca²⁺ flows into the terminal.
- The Ca²⁺ influx triggers synaptic vesicles to fuse with the presynaptic membrane and release neurotransmitter into the synaptic cleft.
- Neurotransmitter diffuses across the cleft and binds receptors on the postsynaptic membrane.
- Receptor binding opens or closes ion channels on the postsynaptic cell, producing a graded excitatory or inhibitory postsynaptic potential.
- The neurotransmitter is cleared — by reuptake, enzymatic breakdown, or diffusion — so the signal does not persist indefinitely.
This one-way, chemically-mediated step is exactly where most CNS-acting drugs work: SSRIs block serotonin reuptake, botulinum toxin blocks vesicle fusion, and neuromuscular blockers occupy the postsynaptic acetylcholine receptor.
Key Neurotransmitters
| Neurotransmitter | Primary role |
|---|---|
| Acetylcholine | Neuromuscular junction transmission; parasympathetic signaling; memory circuits in the CNS |
| Dopamine | Reward and motivation pathways; motor control (substantia nigra); reduced in Parkinson's disease |
| Serotonin | Mood regulation, sleep, appetite; target of SSRIs |
| Norepinephrine | Sympathetic "fight-or-flight" signaling; arousal and attention |
| GABA | Principal inhibitory neurotransmitter in the CNS; target of benzodiazepines and barbiturates |
| Glutamate | Principal excitatory neurotransmitter in the CNS; central to learning and memory (long-term potentiation) |
Central and Peripheral Nervous Systems
The nervous system is organized into two divisions that work together:
- Central Nervous System (CNS) — brain and spinal cord. This is where sensory information is integrated and motor commands are generated.
- Peripheral Nervous System (PNS) — all neural tissue outside the CNS. It is subdivided into the somatic division (voluntary control of skeletal muscle) and the autonomic division (involuntary control of smooth muscle, cardiac muscle, and glands, itself split into sympathetic and parasympathetic branches).
This division matters clinically: a lesion's location tells you which functions are lost. Damage confined to a peripheral nerve produces a focal sensory or motor deficit in that nerve's distribution, while a CNS lesion (e.g., stroke) can affect integration, coordination, or consciousness far beyond a single nerve's territory.
Key Terms
| Term | Definition | Related Concept |
|---|---|---|
| Resting membrane potential | The steady voltage across a neuron's membrane at rest, about -70 mV, maintained by the Na+/K+-ATPase and K+ leak channels | Action potential, ion gradients |
| Threshold | The membrane potential (~-55 mV) that must be reached to trigger an action potential | Depolarization, all-or-none law |
| Depolarization | Membrane potential becomes less negative (more positive) due to Na+ influx | Action potential, EPSP |
| Repolarization | Membrane potential returns toward resting level as K+ exits the cell | Action potential |
| Refractory period | Interval after an action potential during which a new one cannot (absolute) or can only partially (relative) be triggered | Na+ channel inactivation |
| Saltatory conduction | Action potential "jumping" between nodes of Ranvier in myelinated axons, greatly increasing conduction speed | Myelin, nodes of Ranvier |
| Synapse | Junction between two neurons, or a neuron and an effector, where signal transmission occurs | Neurotransmitter, synaptic cleft |
| Neurotransmitter | Chemical messenger released from a presynaptic neuron that alters the postsynaptic membrane potential | Synaptic transmission, receptor binding |
| EPSP / IPSP | Excitatory/inhibitory postsynaptic potential — graded change in postsynaptic membrane potential moving it toward or away from threshold | Synaptic integration |
| Autonomic nervous system | PNS division controlling involuntary functions, divided into sympathetic and parasympathetic branches | CNS/PNS organization |
Common Mistakes
Misconception: The action potential is caused by sodium and potassium simply "switching places" across the membrane.
Why it's wrong: Very few ions actually cross the membrane during a single action potential — nowhere near enough to equalize concentrations. The dramatic voltage change comes from a change in membrane permeability (which channels are open), not from a bulk exchange of ions.
Correct understanding: A single action potential involves a tiny, localized flux of Na+ in and K+ out — enough to flip the local voltage, but the concentration gradients themselves are barely dented. The Na+/K+-ATPase restores any small gradient loss over many cycles; it does not need to "reset" the cell after every single spike.
Misconception: A stronger stimulus produces a bigger action potential.
Why it's wrong: This confuses graded potentials (in dendrites and cell body) with action potentials (in the axon). Action potentials obey the all-or-none law — once threshold is reached, the axon fires a full-amplitude spike, and a stronger stimulus cannot make that individual spike any bigger.
Correct understanding: Stimulus intensity is encoded by frequency of action potentials (rate coding) and by the number of neurons recruited, not by the size of any single action potential.
Misconception: Myelin conducts the electrical signal itself, the way an insulated wire conducts current.
Why it's wrong: Myelin does not conduct the action potential — it is not excitable tissue. The myelinated segments cannot generate a new action potential at all because voltage-gated Na+ channels are concentrated only at the nodes of Ranvier.
Correct understanding: Myelin works by preventing current leakage across the membrane between nodes, so passive current spreads efficiently to the next node, where the signal is actively regenerated. It speeds conduction by letting the signal "skip" the insulated stretches, not by carrying current itself.
Comparison and Connections
| Feature | Chemical Synapse | Electrical Synapse |
|---|---|---|
| Transmission medium | Neurotransmitter diffusing across a cleft | Direct ionic current through gap junctions |
| Speed | Slower (synaptic delay ~0.5–1 ms) | Near-instantaneous |
| Directionality | Unidirectional | Usually bidirectional |
| Signal modification | Can amplify, inhibit, or modulate (excitatory/inhibitory, plasticity) | Signal passed largely unchanged |
| Example location | Most CNS synapses, neuromuscular junction | Cardiac muscle, some brainstem/retinal circuits |
| Clinical relevance | Target of most CNS/PNS-acting drugs | Rarely a direct drug target |
| Feature | Continuous Conduction (Unmyelinated) | Saltatory Conduction (Myelinated) |
|---|---|---|
| Mechanism | Sequential regeneration along the entire membrane | Signal jumps between nodes of Ranvier |
| Speed | ~0.5–2 m/s | Up to ~120 m/s |
| Energy cost | Higher (whole membrane repolarized) | Lower (only nodes repolarized) |
| Example fiber | Pain fibers (C fibers) | Motor neurons, proprioceptive fibers (Aα) |
Practice Questions
Recall
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What is the approximate resting membrane potential of a neuron, and which ion's leak channels are most responsible for setting it? Answer guidance: About -70 mV, set primarily by K+ leak channels (the membrane is far more permeable to K+ than Na+ at rest).
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List the five phases of a typical action potential in order. Answer guidance: Resting state → depolarization → repolarization → hyperpolarization (undershoot) → return to resting potential.
Understanding
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Explain why the action potential is described as "all-or-none." Answer guidance: Once the membrane reaches threshold, voltage-gated Na+ channels open fully and regeneratively, producing a fixed-amplitude spike regardless of how much the stimulus exceeded threshold. Sub-threshold stimuli produce no action potential at all.
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Why does saltatory conduction increase conduction velocity compared to continuous conduction? Answer guidance: Myelin prevents current leak between nodes of Ranvier, so depolarization spreads passively (and quickly) to the next node, where it is actively regenerated. The action potential effectively "jumps" from node to node instead of regenerating along every patch of membrane.
Application
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A local anesthetic blocks voltage-gated Na+ channels near a peripheral nerve. What immediate effect would this have on that nerve's ability to transmit pain signals? Answer guidance: Without functional Na+ channels, the membrane cannot depolarize to threshold, so no action potential can be generated or propagated past the blocked segment — pain signals from that region fail to reach the CNS.
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A patient with multiple sclerosis has progressive demyelination of CNS axons. Explain the physiological basis of the resulting slowed and eventually failed nerve conduction. Answer guidance: Loss of myelin removes the insulation between nodes of Ranvier, allowing current to leak out before reaching the next node. This slows saltatory conduction and, if severe enough, prevents the depolarization from reaching threshold at the next node, blocking conduction entirely.
Analysis
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Compare what happens at the synapse when a drug blocks neurotransmitter reuptake (e.g., an SSRI) versus when a drug blocks the postsynaptic receptor (e.g., a neuromuscular blocker). How do the net effects differ? Answer guidance: Reuptake blockade prolongs and enhances the neurotransmitter's action in the cleft (more/longer receptor binding, increased signaling). Receptor blockade prevents the neurotransmitter from acting at all, regardless of how much is released, producing the opposite functional outcome (reduced signaling) even though both drugs act at the synapse.
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During the absolute refractory period, no stimulus can trigger a new action potential, but during the relative refractory period, an unusually strong stimulus can. Explain the ionic basis of this difference. Answer guidance: In the absolute refractory period, voltage-gated Na+ channels are inactivated (not just closed) and cannot reopen regardless of stimulus strength. In the relative refractory period, Na+ channels have recovered from inactivation, but the membrane is hyperpolarized (K+ channels still open), so it is farther from threshold — a stronger-than-normal depolarizing stimulus can still reach threshold and fire.
FAQ
Why is the resting membrane potential negative rather than zero or positive?
Because the membrane is more permeable to K+ than to any other ion at rest, and K+ diffuses out of the cell down its concentration gradient (it is far more concentrated inside than outside). As positive charge leaves, the inside becomes progressively more negative until the electrical pull back inward roughly balances the chemical push outward. This equilibrium point sits close to -90 mV for K+ alone, and small Na+ leak pulls it up slightly to the observed -70 mV.
Does the action potential use up the neuron's ion gradients each time it fires?
Only trivially. A single action potential moves a tiny fraction of the total Na+ and K+ ions available — the gradients themselves change by a negligible amount. The Na+/K+-ATPase restores this small loss over time, which is why neurons can fire thousands of times without their gradients collapsing, as long as the pump has adequate ATP.
What is the difference between a graded potential and an action potential?
Graded potentials (in dendrites and cell bodies) vary continuously in size with stimulus strength, decay with distance, and can summate. Action potentials (in the axon) are all-or-none, fixed in amplitude, and propagate without decrement over long distances. Graded potentials are how a neuron "decides" whether to fire; the action potential is the fixed, reliable signal it sends once that decision is made.
Why do some drugs target ion channels while others target neurotransmitter receptors?
Because these are two different, druggable steps in the same overall signaling chain. Local anesthetics and some antiarrhythmics target voltage-gated ion channels to block signal generation/propagation. Antidepressants, antipsychotics, and neuromuscular blockers target neurotransmitter reuptake or postsynaptic receptors to modulate signal transmission at the synapse. Knowing which step a drug acts on predicts both its therapeutic effect and its side-effect profile.
How does the autonomic nervous system relate to what happens at the synapse?
The autonomic nervous system's sympathetic and parasympathetic branches release different neurotransmitters (mainly norepinephrine and acetylcholine, respectively) at their target synapses. The same synaptic mechanism — vesicle release, receptor binding, signal termination — applies, but which neurotransmitter is released and which receptor it binds determines whether the effect is, for example, increasing heart rate (sympathetic, beta-1 receptors) or slowing it (parasympathetic, muscarinic receptors).
Quick Revision
- Resting membrane potential ≈ -70 mV, maintained by the Na+/K+-ATPase (3 Na+ out, 2 K+ in) and K+ leak channels
- Threshold for an action potential ≈ -55 mV
- Action potential phases: resting → depolarization (Na+ in) → repolarization (K+ out) → hyperpolarization → return to rest
- Action potentials are all-or-none; stimulus strength is encoded by firing frequency, not spike size
- Absolute refractory period: Na+ channels inactivated, no new spike possible; relative refractory period: possible only with a stronger stimulus
- Myelinated axons use saltatory conduction (signal jumps node to node) — much faster and more energy-efficient than continuous conduction in unmyelinated axons
- Chemical synapses: action potential → Ca2+ influx → vesicle fusion → neurotransmitter release → postsynaptic receptor binding → EPSP or IPSP
- Electrical synapses transmit current directly through gap junctions — faster but less modifiable than chemical synapses
- Major neurotransmitters: acetylcholine (NMJ, memory), dopamine (reward, motor), serotonin (mood), norepinephrine (sympathetic arousal), GABA (main inhibitory), glutamate (main excitatory)
- CNS = brain + spinal cord (integration); PNS = somatic (voluntary) + autonomic (involuntary: sympathetic/parasympathetic)
- Most CNS/PNS-acting drugs work by modifying one specific step: channel function, vesicle release, receptor binding, or neurotransmitter clearance
- Lesion location predicts deficit pattern: peripheral nerve damage = focal deficit; CNS damage = potentially widespread deficits
Related Topics
Prerequisites: Introduction to Physiology, cell membrane structure and transport, basic electrochemistry (ion gradients, Nernst equilibrium)
Related Topics: Muscle Physiology (neuromuscular junction shares the same synaptic mechanism), Endocrine Physiology (hormones vs. neurotransmitters as signaling molecules), Cardiovascular Physiology (autonomic control of heart rate), Pharmacology (drug targets along the neuronal signaling pathway)
Next Topics: Special Senses Physiology, Muscle Physiology, Autonomic Nervous System Physiology
This page is for educational purposes. Always verify with current clinical guidelines.