Membrane Potentials and Ion Channel Physiology

Membrane Potentials

Review & Context

Neurons communicate by changes in their membrane potential (Vm), which are driven by the movement of ions across the cell membrane. These changes are fundamental to neuronal signaling and information processing in the nervous system.

• Membrane potential (Vm): The electrical potential difference across a cell's plasma membrane.

• Membrane current (Im): The flow of ions across the membrane, altering Vm.

• Opening and closing of ion channels regulate Im and Vm.

• Neuronal information processing depends on the diversity and interaction of ion channels.

Properties of Ion Channels

Key Properties

Ion channels are specialized membrane-spanning proteins that control the passage of ions across the cell membrane, influencing electrical signaling.

• Permeability: Determines how many ions can pass through (conductance).

• Selectivity: Determines which ions are allowed (e.g., Na+, K+, Ca2+, Cl-).

• Gating: Refers to what opens or closes the channel (voltage, ligand, mechanical, etc.).

• Ion channels are membrane-spanning proteins.

• Properties depend on amino acid sequence and accessory proteins.

• Diseases caused by ion channel mutations are called channelopathies.

Voltage-Gated Ion Channels

Mechanisms and Properties

Voltage-gated ion channels open or close in response to changes in membrane potential, playing a critical role in action potential generation and propagation.

• Not voltage-gated: Linear current-voltage (I–V) relationship; conductance does not change with voltage.

• Voltage-gated: Slope (conductance) changes with Vm.

• Open/closed states: Channels flicker between open and closed states (observed via patch clamp).

• Conductance changes: Changes in probability of being open (not partial openings).

• Activation gate opens pore; inactivation gate swings in to block pore.

• Different ion channels vary in event and speed of inactivation.

Types of Ionic Currents

Major Ionic Currents

Ionic currents are generated by the movement of specific ions through their respective channels, each with distinct kinetics and roles in neuronal signaling.

• Na+ currents: Fast activation, rapid inactivation.

• K+ currents: Slower activation, little/no inactivation.

• Ca2+ currents: Diverse kinetics.

• Ih currents: Hyperpolarization-activated inward currents.

Action Potentials (APs)

Definition and Function

Action potentials are rapid, all-or-none electrical signals that form the basis of neuronal information coding and transmission.

• Generated by coordinated Na+ and K+ channel activity.

• Basis for neuronal information coding and transmission.

Graded Potentials vs. Action Potentials

Comparison

Neurons utilize both graded and action potentials for signaling, each with distinct properties and functions.

• Graded potentials:

  • Slow, analog, variable amplitude.

  • Usually generated in dendrites or soma.

  • Governed by passive membrane properties (time constant, resistance, capacitance).

• Action potentials:

  • Fast, digital, all-or-none.

  • Fixed amplitude (for a given neuron).

  • Generated in axons.

Threshold & Firing

Initiation of Action Potentials

Action potentials are triggered when graded potentials reach a critical threshold, leading to rapid depolarization.

• Graded potentials reaching threshold trigger AP.

• Threshold is determined by the properties of voltage-gated Na+ channels.

Ionic Mechanisms of APs

Experimental Insights

Classic experiments (e.g., Hodgkin & Huxley, squid giant axon) revealed the ionic basis of action potentials.

• Voltage clamp: Holds Vm constant, records changes in Im to reveal changes in conductance.

Ionic Currents During APs

• Fast inward current: Na+ influx (activates, then inactivates quickly).

• Slower outward current: K+ efflux (activates slowly, stays on, no inactivation).

• Pharmacological blockers:

  • TTX (blocks Na+): Isolates Na+ current.

  • TEA (blocks K+): Isolates K+ current.

Refractory Periods

Types and Functions

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

• Absolute refractory period: Na+ channels inactivated; no stimulus can trigger another AP.

• Relative refractory period: Some Na+ channels recovered, many K+ channels still open; stronger-than-normal stimulus needed.

Positive Feedback Cycle

Mechanism in AP Initiation

Positive feedback is a key mechanism in the explosive initiation of action potentials.

• Axon hillock has high Na+ channel density.

• Once threshold is crossed, explosive Na+ channel activation leads to depolarization, recruiting more Na+ channels.

• Example of positive feedback in biology.

Speed of Propagation

Factors Affecting Conduction Velocity

The speed at which action potentials propagate depends on axon diameter, membrane properties, and myelination.

• Squid giant axon: ~45 mph.

• Rat optic nerve: ~30 mph.

• Primate corticospinal axon: ~100 mph.

• Shrimp giant fiber: ~450 mph.

• Conduction velocity equation: $v = \frac{1}{\sqrt{(\text{axial resistance} \times \text{membrane capacitance})}}$

  • Decrease axial resistance → ↑ speed (larger axon diameter).

  • Decrease membrane capacitance → ↑ speed (thicker membrane).

Myelination

Role in AP Conduction

Myelin increases the speed and efficiency of action potential propagation in vertebrate nervous systems.

• Myelin increases effective membrane thickness → ↓ capacitance → ↑ speed.

• Nodes of Ranvier = unmyelinated gaps where AP is regenerated.

• AP appears to "jump" from node to node = saltatory conduction.

• Demyelinating diseases (e.g., Multiple Sclerosis) impair conduction, causing major clinical deficits.

Key Takeaways

• Ion channel properties (permeability, selectivity, gating) shape neuronal function.

• APs = fast, all-or-none signals generated by coordinated Na+ and K+ channel activity.

• Refractory periods ensure unidirectional propagation and limit firing frequency.

• AP conduction speed depends on axon diameter and myelination.

• Myelination enables rapid signaling in compact vertebrate nervous systems.

Table: Comparison of Major Ion Channel Properties

Property	Na+ Channel	K+ Channel	Ca2+ Channel
Activation Speed	Fast	Slow	Diverse
Inactivation	Rapid	Little/None	Diverse
Role in AP	Depolarization	Repolarization	Signaling, neurotransmitter release