Neurophysiology: Membrane Potentials and Action Potentials

The Nervous System: Membrane Potentials and Action Potentials

Membrane Potentials

Neurons are highly excitable cells that rely on changes in membrane potential to transmit signals. The resting membrane potential is a fundamental property that distinguishes neurons from most other cell types.

• Resting membrane potential: The electrical potential difference across the plasma membrane when the cell is not actively sending a signal, typically around -70 mV in neurons.

• Excitability: Neurons can rapidly change their membrane potential in response to stimuli, enabling communication throughout the nervous system.

Basic Principles of Electricity in Neurons

Electrical signals in neurons are generated and propagated by the movement of ions through specialized membrane channels.

• Membrane ion channels: Large protein structures that allow specific ions to pass through the membrane.

• K+ ion channel: A channel selective for potassium ions, crucial for setting the resting membrane potential.

• Two main types of ion channels:

  • Leakage (nongated) channels: Always open, allowing ions to move down their concentration gradients.

  • Gated channels: Open or close in response to specific stimuli. Three main types:

    • Chemically gated (ligand-gated) channels: Open in response to binding of a chemical messenger (e.g., neurotransmitter).

    • Voltage-gated channels: Open in response to changes in membrane potential.

    • Mechanically gated channels: Open in response to physical deformation of the receptor (e.g., touch).

Measuring Membrane Potential

The membrane potential is measured using electrodes, with a voltmeter indicating the difference in charge between the inside and outside of the cell.

• Microelectrode: Inserted inside the cell to measure internal voltage.

• Ground electrode: Placed outside the cell as a reference.

• Typical resting membrane potential: -70 mV (inside negative relative to outside).

Generating the Resting Membrane Potential

The resting membrane potential is established by differences in ion concentrations and membrane permeability.

• Differences in ionic composition:

  • ICF (intracellular fluid): High K+, low Na+

  • ECF (extracellular fluid): High Na+, low K+

  • K+: Plays the most important role in setting the membrane potential due to its high permeability.

• Differences in plasma membrane permeability:

  • Impermeable to large anionic proteins (remain inside cell).

  • Slightly permeable to Na+ (few leakage channels).

  • Quite permeable to Cl-.

  • 25 times more permeable to K+ than Na+ (many K+ leakage channels).

  • More K+ diffuses out than Na+ diffuses in, making the inside of the cell negative.

• Sodium-potassium pump (Na+/K+ ATPase):

  • Actively transports 3 Na+ out and 2 K+ in per ATP hydrolyzed.

  • Stabilizes and maintains the resting membrane potential.

Equation for Nernst Potential (for K+):

$E_K = \frac{RT}{zF} \ln \left( \frac{[K^+]_{out}}{[K^+]_{in}} \right)$

Additional info: The Nernst equation calculates the equilibrium potential for a particular ion based on its concentration gradient.

Changing the Resting Membrane Potential

Membrane potential can change due to alterations in ion concentrations or membrane permeability, producing electrical signals.

• Types of signals:

  • Graded potentials: Localized, short-lived changes in membrane potential.

  • Action potentials: Long-distance signals that propagate along the axon.

• Depolarization: The inside of the membrane becomes less negative (more positive) compared to resting potential; increases probability of generating an action potential.

• Hyperpolarization: The inside of the membrane becomes more negative compared to resting potential; decreases probability of generating an action potential.

Graded Potentials

Graded potentials are brief, localized changes in membrane potential, typically occurring in dendrites and cell bodies.

• Triggered by: Stimuli that open gated ion channels.

• Signal strength: Varies with stimulus intensity; can be summed.

• Types:

  • Receptor potential (generator potential): Occurs in sensory receptors.

  • Postsynaptic potential: Occurs in postsynaptic neurons.

Action Potentials

Action potentials (APs) are rapid, long-lasting electrical signals that travel along axons, enabling communication between distant parts of the nervous system.

• All-or-none phenomenon: APs occur only if the membrane potential reaches threshold; otherwise, no AP is generated.

• Nerve impulse: The propagation of an AP along the axon.

• Specific channels: Voltage-gated Na+ and K+ channels must open in sequence.

Ion Channel Mechanisms in Action Potentials

Voltage-gated sodium and potassium channels are essential for the generation and propagation of action potentials.

• Sodium channels: Have two gates:

  • Activation gate: Opens rapidly in response to depolarization.

  • Inactivation gate: Closes shortly after activation, stopping Na+ influx.

• Potassium channels: Have a single voltage-activated gate that opens more slowly in response to depolarization.

Steps in Generating an Action Potential

The action potential consists of four main phases, each corresponding to changes in ion channel states and membrane potential.

1. Resting state: All voltage-gated Na+ and K+ channels are closed; steady state maintained by leakage channels and Na+/K+ pump.

2. Depolarization: Voltage-gated Na+ channels open, Na+ enters the cell, causing rapid rise in membrane potential.

3. Repolarization: Na+ channels inactivate, K+ channels open, K+ exits the cell, restoring negative membrane potential.

4. Hyperpolarization: Some K+ channels remain open, causing membrane potential to become more negative than resting; Na+ channels reset.

After repolarization: The Na+/K+ ATPase restores ion gradients.

Threshold and the All-or-None Phenomenon

Not all depolarizations result in action potentials. The membrane must reach a critical threshold for an AP to be initiated.

• Threshold: The membrane potential at which voltage-gated Na+ channels open en masse, triggering the AP.

• Positive feedback: Na+ influx causes further depolarization, opening more Na+ channels.

• All-or-none: If threshold is reached, the AP is generated and propagated; if not, no AP occurs.

Propagation of an Action Potential

Once initiated, the action potential propagates along the axon, allowing rapid communication.

• Depolarization: Na+ influx at one segment triggers depolarization in adjacent segments.

• Directionality: APs move in one direction due to refractory periods and voltage sensitivity of Na+ channels.

• Myelinated vs. unmyelinated axons: Propagation mechanisms differ, affecting speed and efficiency.

Refractory Periods

Refractory periods ensure unidirectional propagation and limit the frequency of action potentials.

• Absolute refractory period: No new AP can be initiated, regardless of stimulus strength (Na+ channels inactivated).

• Relative refractory period: A stronger-than-usual stimulus can initiate another AP (some Na+ channels reset, K+ channels still open).

Conduction Velocity

The speed at which action potentials travel along axons depends on several factors.

• Factors affecting conduction velocity:

  • Axon diameter: Larger diameter = faster conduction.

  • Degree of myelination: Myelinated axons conduct faster due to saltatory conduction.

• Continuous conduction: Occurs in unmyelinated axons; AP moves along every part of the membrane.

• Saltatory conduction: Occurs in myelinated axons; AP jumps from node to node (nodes of Ranvier), greatly increasing speed.

Classification of Nerve Fibers

Nerve fibers are classified based on diameter, myelination, and conduction speed.

Group	Diameter	Myelination	Conduction Speed	Function
Group A	Largest	Myelinated	150 m/s (~300 mph)	Somatic sensory and motor fibers (skin, skeletal muscles, joints)
Group B	Intermediate	Lightly myelinated	15 m/s (~30 mph)	Visceral sensory and motor fibers
Group C	Smallest	Unmyelinated	1 m/s (~2 mph)	Visceral sensory and motor fibers

Additional info: Groups B and C include autonomic nervous system (ANS) fibers serving visceral organs.