An electrophysiological technique in which the voltage of a cell membrane is controlled experimentally, and the current passing across the membrane is measured.

Current clamp

Neuronal Action Potential - Pharmacological Inhibition of Na⁺ and K⁺ Channels

The difference in electrical potential between two points.

All-or-nothing is usually used when describing the action potential. It refers to the well-known observation that an action potential always occurs in its full size (i.e., full magnitude of voltage change).

Many physiologists use all-or-nothing and all-or-none interchangeably.

Important Features of the Neuronal Action Potential

Proposed model for the inactivation of some voltage-gated ion channels. According to this model, after channel opening, the pore of the open channel is plugged by a globular cytoplasmic portion of the channel protein. The globular portion (ball of amino acids) is tethered to the rest of the protein by a linker part (chain of amino acids).

Channel inactivation

Neuronal Action Potential - Important Features of the Neuronal Action Potential

An integral membrane protein which contains a pore through which ions, water, or polar molecules permeate. For any given channel, the pore is usually very selective for the particular ion or molecule. For example, sodium (Na⁺) channels are very selective for Na⁺ over other cations.

The channel pore may be constitutively open, or it may be gated to the open state by various stimuli such as chemical ligands, voltage, temperature, or mechanical stimulation of the membrane.

An electrophysiological technique in which the current passing across the cell membrane is controlled experimentally, and the membrane voltage is measured.

Voltage clamp

Neuronal Action Potential - Pharmacological Inhibition of Na⁺ and K⁺ Channels

V_DF

When an ion is not at its electrochemical equilibrium, an electrochemical driving force (V_DF) acts on the ion, causing the net movement of the ion across the membrane down its own electrochemical gradient.

The electrochemical driving force is generally expressed in millivolts and is calculated according the following equation:

V_DF = V_m − V_eq

where V_DF is the electrochemical driving force, V_m is the membrane potential, and V_eq is the equilibrium potential.

Membrane potential
Equilibrium potential
Electrochemical gradient

Resting Membrane Potential - Electrochemical Driving Force Acting on Ions
Electrochemical Driving Force Calculator

Electrophysiology is the study of the electrical properties of biological macromolecules, cells, tissues, and organs. Electrical signals such as voltage and/or current are generally measured. Examples include measuring changes in the membrane voltage of excitable cells (e.g., neurons, muscle cells, and some endocrine cells) during an action potential. The current carrried by ions as they permeate the pore of ion channels can also be measured - both at the single-channel level (single-channel current), as well as the macroscopic current resulting from the activity of a population of channels. As another example, electrical measurements may involve recording voltage changes at the surface of the skin that result from the activity of skeletal muscles (electromyogram, EMG), cardiac myocytes (electrocardiogram, ECG), or neurons in the brain (electroencephalogram, EEG).

The Hodgkin cycle represents a positive feedback loop in neurons, where an initial membrane depolarization from the resting value (∼ −70 mV) to the threshold value (∼ −50 mV) leads to rapid depolarization of the membrane potential to approach the equilibrium potential for Na⁺ (V_Na ≈ +60 mV). The voltage-gated Na⁺ channels of neurons are responsible for the Hodgkin cycle.

See the figure depicting the Hodgkin cycle.

Important Features of the Neuronal Action Potential

Lidocaine is a local anesthetic and an antiarrhythmic drug. It is a commonly used local anesthetic for minor surgery and in dental procedures. Lidocaine is also used topically to relieve itching, burning, and pain from skin inflammations.

Lidocaine's mechanism of action is to block fast voltage-gated Na⁺ channels of neurons and cardiac myocytes.

Other names used for lidocaine are xylocaine and lignocaine.

Pharmacological Inhibition of Na⁺ and K⁺ Channels

Lidocaine (Wikipedia)

The voltage difference across a cell plasma membrane.

The membrane potential is generally inside negative with respect to the outside, where the outside potential is generally set as the reference value. In electrically excitable cells, the value of the membrane potential can be positive (inside with respect to the outside) during electrical activity (i.e., during action potentials).

Resting membrane potential

Resting membrane potential

Neurotoxins are chemical molecules that have an adverse effect on neuron function and, thus, disrupt the normal function of the nervous system. Neurotoxins could be small molecules or peptides and can be derived from a variety of invertebrate and vertebrate animals, as well as plant species.

The following is a short list of some examples of neurotoxins:

α-Bungarotoxin: A peptide neurotoxin that inhibits the nicotinic acetylcholine receptor.

Chlorotoxin: A peptide neurotoxin that inhibits chloride channels.

α-Conotoxin: A peptide neurotoxin that inhibits the nicotinic acetylcholine receptor.

δ-Conotoxin: A peptide neurotoxin that inhibits voltage-gated sodium channels.

w-Conotoxin: A peptide neurotoxin that inhibits N-type voltage-gated calcium channels.

Picrotoxin: Inhibits GABA_A receptor chloride channels.

Tetrodotoxin: Inhibitor of neuronal voltage-gated sodium channels.

A local topical anesthetic.

Procaine's mechanism of action is to block fast voltage-gated Na⁺ channels of neurons.

Pharmacological Inhibition of Na⁺ and K⁺ Channels

Procaine (Wikipedia)

The voltage difference across a cell plasma membrane in the resting or quiescent state. It is also simply referred to as the resting potential (V_rest). The value of the resting membrane potential varies from cell to cell. Depending on the cell type, it can range from −90 mV to −20 mV.

For example, V_rest is −90 mV in skeletal and cardiac muscle cells as well as in astrocytes. In a typical neuron, V_rest is approximately −70 mV. In many non-excitable cells, V_rest ranges from −60 to −50 mV. In photoreceptors, V_rest is about −20 mV.

Resting membrane potential

A rectangular signal waveform used in physiological studies to perturb (i.e., challenge) the system under study. The response of the system to the pulse is then studied carefully to learn about how the system responds to challenges.

Examples include pulses of voltage or current in electrophysiological experiments. Other examples include pulses of light, pressure, temperature, ligand, etc.

A square-wave pulse is defined by the amplitude and duration of the pulse, as well as by the frequency at which the pulse is applied to the system under study.

Neuronal Action Potential - Introduction

Square wave (Wikipedia)

Sub-threshold (or subthreshold) refers to a stimulus that is too small in magnitude to produce an action potential in excitable cells.

In general, a sub-threshold stimulus leads to the depolarization of the membrane, but the magnitude of the depolarization is not large enough to reach the threshold voltage. Therefore, sub-threshold stimuli do not elicit action potentials.

Threshold
Supra-threshold

Neuronal Action Potential - Introduction

Supra-threshold (or suprathreshold) refers to a stimulus that is large enough in magnitude to produce an action potential in excitable cells.

In general, a supra-threshold stimulus leads to the depolarization of the membrane, and the magnitude of the depolarization is larger than that necessary to simply reach the threshold voltage. Therefore, supra-threshold stimuli elicit action potentials.

Threshold
Sub-threshold

Neuronal Action Potential - Introduction

TEA

An inhibitor of voltage-gated potassium (K⁺) channels.

TEA is a quaternary ammonium cation (positively charged ion). It is also commonly used as a cation replacement for sodium (Na⁺) in physiological buffers used in ion replacement experiments.

Pharmacological Inhibition of Na⁺ and K⁺ Channels

TTX

Inhibitor of fast voltage-gated sodium (Na⁺) channels of neurons and muscle cells. It is an extremely potent and toxic neurotoxin.

Pharmacological Inhibition of Na⁺ and K⁺ Channels

Tetrodotoxin (Wikipedia)

The membrane voltage that must be reached in an excitable cell (e.g., neuron or muscle cell) during a depolarization in order to generate an action potential. At the threshold voltage, voltage-gated channels become activated. Threshold is approximately −50 to −40 mV in most excitable cells.

Sub-threshold
Supra-threshold

Neuronal Action Potential - Introduction