Membrane Potential, Resting Potential, and Action Potentials in Giant Squid Axon
Giant squid axon and electrical signaling: key ideas
Giant squid nerve cells and their axons are unusually large, giving researchers an accessible preparation to study electrical signals in the nervous system.
The squid nervous system includes brain and sequential (first, second, and third order) neurons connected in series; the third-order neuron is highlighted in red.
The axon diameter is about 800 micrometers, roughly the size of a phone charging cable; this is more than 100 times larger than many human axons, which makes recording and manipulating signals easier.
Because of their size, these axons have been used extensively, and continue to be used, to study how electrical signals propagate in neurons.
Measurements and terminology
Membrane potential changes are expressed in millivolts (mV).
Stimulation of a neuron is achieved by injecting current into the cell; current is measured in amperes (A).
The recording setup can show resting membrane potential and action potentials, as well as different voltage traces depending on the type of stimulation.
The bottom axis/trace typically shows the membrane potential; the stimulating current trace is often shown in a different color (e.g., yellow/orange) and can go below zero (negative current).
Types of membrane potential changes observed in neurons
Receptor potential: a depolarization seen in a sensory neuron when it is stimulated by a sensory input.
Synaptic potential: a change caused by activation of a synapse; a presynaptic neuron (blue) forms a synapse with the recorded neuron, triggering a potential.
Action potential: initiated near the axon hillock (close to the cell body) when a stimulus pushes the membrane potential across the threshold, resulting in a spike.
Action potentials are the primary mechanism by which neurons encode information in many pathways.
A practical application mentioned
Local anesthetics used by dentists illustrate how altering membrane potential and nerve excitability can affect sensation and pain.
Core components that determine membrane potential
The membrane must be present to separate inside from outside.
Ion channels: selective pores in the membrane that allow specific ions to pass, contributing to permeability.
Active transporters (pumps): proteins that bind ions and move them across the membrane against their concentration gradient, consuming energy (e.g., ATP).
Passive ion flow through channels: ions move down their electrochemical gradient when channels are open.
Ions highlighted: potassium (K⁺), sodium (Na⁺), chloride (Cl⁻) as key contributors to the resting potential and action potential dynamics.
The arrangement creates a membrane potential by establishing and maintaining concentration gradients and selective permeabilities.
Concept of ion gradients and electrochemical gradients
Ion concentration gradients (more of some ions on one side of the membrane than the other) are established by pumps and channels.
The electrochemical gradient has two components: a chemical gradient (concentration difference) and an electrical gradient (charge difference across the membrane).
The net flux of ions is governed by both the gradient and the membrane’s permeability to those ions.
A simple model to illustrate the setup
A membrane separates the inside from the outside of the cell.
If potassium channels are permeable to K⁺, K⁺ tends to move down its concentration gradient from inside to outside.
At a given membrane voltage, ions may also flow back in the opposite direction if the electrical force opposes the chemical gradient, leading toward an electrochemical equilibrium.
Electrochemical equilibrium is the state with no net ion flux.
Resting membrane potential and multi-ion considerations
Real neurons have several ions with unequal intracellular vs. extracellular concentrations (e.g., K⁺, Na⁺, Cl⁻).
The resting membrane potential is determined by a combination of gradients and permeabilities of these ions; it is not carried by a single ion, but by their combined influence.
A single-ion view (e.g., pure Nernst for K⁺ alone) is insufficient for the resting potential in real neurons.
How to think about the resting potential with multiple ions
The Goldman-Hodgkin-Katz (GHK) framework (a generalization of the Nernst concept) accounts for multiple ions and their permeabilities:
Goldmann equation (conceptual form):
Vm = rac{RT}{F} \, rac{ igl(P{K}[K^+]o + P{Na}[Na^+]o + P{Cl}[Cl^-]iigr) }{ igl(P{K}[K^+]i + P{Na}[Na^+]i + P{Cl}[Cl^-]_oigr) } \text{(in log form, the full expression uses a natural log or log base 10 with a factor)}
In practice, a frequently cited simplified form uses base-10 logarithms and is temperature dependent; the constants change with room vs body temperature, but the qualitative dependence is the same.
The resting polarity is dominated by the relative permeabilities and gradients of K⁺, Na⁺, and Cl⁻; at typical mammalian resting states, neurons are about -60 to -70 mV, with -58 mV given as an example in the material.
Na⁺, K⁺, and Cl⁻ gradients you should know
Potassium (K⁺): high inside, low outside; drives resting potential via outward leak when channels are open.
Sodium (Na⁺): high outside, low inside; influx during depolarization increases membrane potential toward Na⁺’s equilibrium potential during an action potential.
Chloride (Cl⁻): typically higher outside in many neurons; its permeation tends to hyperpolarize but can also contribute to depolarizing events depending on gradients and receptor types.
How the resting potential is established and maintained
Initially, a concentration gradient exists due to pumps moving ions against their gradient (active transporters).
Membrane permeability to ions (via channels) determines which ions have the strongest influence on the resting potential.
Permeability for potassium is a major driver because K⁺ channels are relatively leaky, promoting K⁺ efflux and negative interior potential.
The resting potential is a balance between outward driving force (e.g., K⁺ leaving) and inward driving forces (e.g., Na⁺ entering and Cl⁻ behavior), leading to a steady negative value.
How changes in permeability or gradients affect the membrane potential
If permeability to a particular ion increases (e.g., Na⁺ channels opening during an action potential), the membrane potential shifts toward that ion’s equilibrium potential.
When the permeability changes while gradients remain, the attainable range of membrane potentials is anchored by the equilibrium potentials of the ions involved.
If the normal line for an ion’s equilibrium potential shifts (e.g., due to altered gradients), the resting or action potential levels shift accordingly.
The four phases of the action potential (neuron-specific schematic reference)
Phase 1: Rising phase (depolarization) – a sharp increase in Na⁺ permeability causes a rapid depolarization toward the Na⁺ equilibrium potential; a sharp spike occurs when threshold is crossed.
Phase 2: Peak and early repolarization – Na⁺ channels begin inactivation; Na⁺ influx slows; K⁺ channels begin to contribute to repolarization.
Phase 3: Repolarization – increased K⁺ permeability drives the membrane back toward a more negative value.
Phase 4: Resting potential and possible hyperpolarization – membrane potential returns to the resting level; there may be a brief hyperpolarization before stabilizing.
Key conceptual points about action potentials
Action potentials are a mechanism by which neurons encode information because they reliably propagate along axons once initiated.
The initiation site is typically near the axon hillock where the integration of excitatory/inhibitory inputs occurs.
Threshold: a critical level of depolarization that must be reached to trigger an action potential; crossing the threshold engages a positive feedback loop that drives the spike.
Why the squid preparation remains relevant today
It provides an accessible model to illustrate fundamental principles of neuronal signaling that apply across species, including humans.
The large size simplifies instrumentation and data collection, helping to elucidate the relationship between membrane potential, ion gradients, and action potentials.
Connections to broader principles and real-world relevance
The interplay between ion gradients and selective permeability is a foundational concept in neurophysiology, linking to topics such as synaptic transmission, neural coding, and pharmacological modulation.
Understanding these processes helps explain clinical phenomena like anesthetic action, nerve conduction block, and how neurons communicate across synapses and networks.
Metaphors and hypothetical scenarios to cement understanding
Think of the cell membrane as a selectively permeable barrier with tiny gates (ion channels) and powered pumps (active transporters) that maintain a chemical and electrical balance across the gate.
The resting state is like a battery at a steady voltage set by what gates are open most of the time and what ions are available on each side.
An action potential is like a coordinated wave of gate openings that travels along the axon, carrying information without diminishing as it propagates.
Equations and numerical references to memorize
Nernst equation (single ion):
E{ion} = rac{RT}{zF} \, ext{ln} \left(\frac{[ion]{outside}}{[ion]_{inside}}\right)
Simplified (approximate at 37°C):
E{ion} \approx \frac{61.5\text{ mV}}{z} \; \log{10} \left(\frac{[ion]{outside}}{[ion]{inside}}\right)
Goldman-Hodgkin-Katz (multi-ion, qualitative representation):
Vm = \frac{RT}{F} \ln \left( \frac{PK[K^+]o + P{Na}[Na^+]o + P{Cl}[Cl^-]i}{PK[K^+]i + P{Na}[Na^+]i + P{Cl}[Cl^-]_o} \right)
Resting membrane potential example: approximately V_m \approx -58 \text{ mV} in the provided slide context.
Summary takeaway
The giant squid axon has been and remains a powerful model for understanding how ion gradients, membrane permeability, and ion transporters shape resting and action potentials.
The resting potential emerges from a balance of gradients and permeabilities across multiple ions; action potentials arise from rapid, temporary shifts in permeability (notably Na⁺) that drive the membrane toward the Na⁺ equilibrium potential, followed by K⁺-driven repolarization.
This framework connects molecular components (channels and pumps) to macroscopic electrical signals that underlie nervous system function and information processing.