Source: Chapter 5, Lecture slides
Tags: action potential, resting potential, membrane potential, ion channels, ion pumps, sodium-potassium pump, depolarization, hyperpolarization, voltage-gated channels, myelin, saltatory conduction, nodes of Ranvier, Hodgkin, Huxley, axon hillock, refractory period, multiple sclerosis
This lecture explains how neurons generate and propagate electrical signals. It covers the ionic basis of the resting membrane potential, the mechanism of the action potential, the roles of voltage-gated ion channels and the sodium-potassium pump, and how myelin speeds signal conduction along the axon.
William James (revisited)
Advocated a science of mind based on three pillars: study of behaviour (psychology), study of biological underpinnings (neurobiology), and study of mental phenomena themselves (introspection). The first two are well developed; the third remains underdeveloped.
Diffusion
The net movement of molecules or atoms from a region of high concentration to a region of low concentration.
Semipermeable membrane
A biological membrane that allows certain molecules or ions to pass through, by diffusion, facilitated diffusion, passive transport, or active transport.
Ion channel
A protein in the cell membrane that forms a selective pore ("selective hole") allowing specific ions to flow through. Passive, meaning no energy (ATP) is required. Functions include establishing the resting membrane potential and shaping action potentials.
Ion pump
A membrane protein that uses energy (ATP) to move ions against their concentration gradient. The sodium-potassium pump is the key example in neurons.
ATP (adenosine triphosphate)
The biochemical molecule used to store and transfer energy in cells.
Membrane potential
The electrical potential difference between the inside and outside of a cell. In neurons, changes in membrane potential are used to code and transmit information.
Resting potential
The membrane potential of a neuron at rest, approximately -65 mV. The minus sign indicates the inside of the cell is negative relative to the extracellular fluid. Only a very small number of ions need to be separated across the membrane to create this potential.
Depolarisation
When the membrane potential becomes less negative (more positive). Occurs when Na⁺ voltage-gated ion channels open and sodium ions flow inward.
Hyperpolarisation
When the membrane potential becomes more negative (further from threshold). Occurs when K⁺ voltage-gated ion channels open and potassium ions flow outward.
Action potential
A rapid, transient change in membrane voltage along an axon. The membrane potential rapidly rises (depolarisation) and then falls (repolarisation). Caused by the sequential opening and closing of voltage-gated Na⁺ and K⁺ channels. Propagates as a wave along the axon.
Voltage-gated ion channel
An ion channel protein found primarily along the axon membrane that opens and closes in response to changes in membrane voltage. Na⁺ and K⁺ voltage-gated channels are central to the action potential.
Firing threshold
The membrane potential (between -50 and -55 mV, variable) at which an action potential is triggered. A neuron's resting potential can be shifted to increase or decrease the likelihood of reaching threshold.
Axon hillock
The specialised region of the neuron cell body where the axon begins. Known as the "trigger zone" because it sums all inhibitory and excitatory inputs and decides whether to fire an action potential. The last site where synaptic potentials are summated before being transmitted to the axon.
Refractory period
After the voltage-gated Na⁺ and K⁺ channels have been triggered, they require several milliseconds to return to a state that can be triggered again. This prevents the signal from bouncing back along the axon in both directions.
Myelin
Layers of lipid bilayer membrane (containing cholesterol) wrapped around axons that act as insulation. Action potentials cannot propagate where the axon is covered in myelin.
Oligodendrocyte
Produces myelin in the CNS.
Schwann cell
Produces myelin in the PNS.
Nodes of Ranvier
Gaps in the myelin sheath along a myelinated axon where the axon membrane is exposed and enriched in ion channels. These nodes allow the action potential to be regenerated, enabling saltatory conduction.
Saltatory conduction
The propagation of action potentials along myelinated axons by jumping from one node of Ranvier to the next. This significantly increases conduction velocity compared to unmyelinated axons.
Sodium-potassium pump (Na⁺/K⁺ ATPase)
An active transporter that pumps 3 Na⁺ ions out of the cell for every 2 K⁺ ions pumped in, both against their concentration gradients. Requires ATP. Establishes and maintains the resting membrane potential. The reverse process is spontaneous.
Multiple sclerosis
An autoimmune disease that breaks down myelin on axons, impairing nerve conduction. Symptoms are variable and can include motor or sensory neuron damage.
Alan Hodgkin and Andrew Huxley
Made direct measurements of voltage changes across an axon membrane during action potentials, using squid giant axons (large enough to insert a voltmeter electrode). Proposed a comprehensive description of action potential propagation. Their theory predicted the existence of voltage-gated ion channels before these were experimentally discovered.
Major ions relevant to neural function: Na⁺, K⁺, Cl⁻, Ca²⁺
Outside the neuron: high concentrations of Na⁺, Cl⁻, Ca²⁺
Inside the neuron: high concentration of K⁺
These concentration gradients are maintained by the sodium-potassium pump and the selective permeability of the membrane
At rest, the inside of the neuron is approximately -65 mV relative to the outside
This is maintained by the Na⁺/K⁺ pump (3 Na⁺ out, 2 K⁺ in) and by leak channels
Only a very small number of ions need to be separated across the membrane to produce this voltage
A stimulus depolarises the membrane at the axon hillock
If the depolarisation reaches the threshold (around -50 to -55 mV), voltage-gated Na⁺ channels open
Na⁺ rushes into the cell, rapidly depolarising the membrane (the rising phase)
Na⁺ channels inactivate; voltage-gated K⁺ channels open
K⁺ flows out of the cell, repolarising the membrane (the falling phase)
The membrane may briefly hyperpolarise before returning to resting potential
The Na⁺/K⁺ pump restores the original ion gradients over time
The action potential generated at the axon hillock propagates as a wave along the axon
Inward current at one point depolarises adjacent membrane, triggering the next action potential
The refractory period ensures the signal travels in one direction only (away from the cell body)
Myelin insulates sections of the axon, preventing ion exchange in those regions
Nodes of Ranvier are the gaps between myelin segments, rich in voltage-gated ion channels
The action potential "jumps" from node to node (saltatory conduction), greatly increasing speed
Oligodendrocytes myelinate in the CNS; Schwann cells myelinate in the PNS
The brain uses approximately 20% of the body's total energy
Most of this energy fuels the electrical impulses neurons use to communicate
Used squid giant axons because they were large enough to insert electrodes
Measured voltage changes during action potentials directly
Their mathematical model predicted voltage-gated ion channels years before they were experimentally observed
Both later worked on war-related projects (radar development)
Resting potential: approximately -65 mV (inside negative relative to outside)
Threshold: approximately -50 to -55 mV
Na⁺/K⁺ pump ratio: 3 Na⁺ out for every 2 K⁺ in (net movement of one positive charge outward per cycle)
⚠️ Know the ion distributions: Na⁺, Cl⁻, Ca²⁺ concentrated outside; K⁺ concentrated inside.
⚠️ Understand the sequence of events in an action potential: threshold reached, Na⁺ channels open (depolarisation), Na⁺ channels inactivate, K⁺ channels open (repolarisation), brief hyperpolarisation, return to rest.
⚠️ The refractory period prevents bidirectional signal propagation.
⚠️ Saltatory conduction is faster than continuous conduction because the action potential jumps between nodes of Ranvier.
⚠️ The Na⁺/K⁺ pump moves 3 Na⁺ out and 2 K⁺ in per cycle, using ATP.
⚠️ Multiple sclerosis is an autoimmune attack on myelin, not on the neurons themselves.
⚠️ Hodgkin and Huxley predicted voltage-gated ion channels before they were discovered.
Q: What is the resting membrane potential of a typical neuron, and why is it negative?
A: Approximately -65 mV. It is negative because the Na⁺/K⁺ pump moves more positive charge out than in (3 Na⁺ out, 2 K⁺ in), and because the membrane is more permeable to K⁺ at rest, allowing K⁺ to leak outward.
Q: What happens when the membrane potential reaches threshold?
A: Voltage-gated Na⁺ channels open, Na⁺ rushes into the cell, and the membrane rapidly depolarises, initiating an action potential.
Q: What is the refractory period, and why does it matter?
A: The refractory period is the several-millisecond interval after an action potential during which voltage-gated channels cannot be re-triggered. It ensures the action potential propagates in one direction along the axon.
Q: How does saltatory conduction increase the speed of signal propagation?
A: Myelin insulates stretches of the axon, so the action potential jumps between nodes of Ranvier (where ion channels are concentrated) rather than travelling continuously along every point of the membrane.
Q: What does the Na⁺/K⁺ pump do, and does it require energy?
A: It pumps 3 Na⁺ out and 2 K⁺ in per cycle, both against their concentration gradients. Yes, it requires ATP.
Q: What organism did Hodgkin and Huxley use for their action potential experiments, and why?
A: Squid giant axons, because their diameter was large enough to allow insertion of a voltmeter electrode inside a functioning axon.
Action potential, resting potential, membrane potential, depolarisation, hyperpolarisation, repolarisation, threshold, voltage-gated ion channel, sodium channel, potassium channel, Na⁺/K⁺ ATPase, sodium-potassium pump, ion channel, ion pump, ATP, diffusion, semipermeable membrane, axon hillock, trigger zone, refractory period, myelin, myelination, oligodendrocyte, Schwann cell, node of Ranvier, saltatory conduction, multiple sclerosis, Hodgkin, Huxley, squid giant axon, brain energy use, MCB C61, UC Berkeley