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.

An early sexual maturation stage, occurring 1 or 2 years before the onset of puberty, during which the zona reticularis of the adrenal cortex releases increased levels of dehydroepiandrosterone (DHEA) and androstenedione. These adrenal androgens are ultimately responsible for the appearance of pubic and axillary hair, increased oil production by facial skin, acne, and distinct adult body odor.

Menarche
Pubarche
Thelarche

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

A deficit in expressing or understanding language.

Disorders of language resulting from damage to areas of the brain responsible for language formation and comprehension.

The ability of a tissue or organ to regulate its own function without extrinsic neural or hormonal input.

For example, in the kidneys, autoregulation ensures relatively constant blood flow and pressure through the kidney tubules in order to maintain a fairly constant glomerular filtration rate (GFR).

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

CO

Cardiac output is defined as the volume of blood pumped every minute by each (left or right) ventricle of the heart. It is generally reported in L/min or mL/min.

Cardiac output (CO) is the product of heart rate (HR) and stroke volume (SV). Thus,

CO = HR × SV

Heart rate is defined as the number of heart contractions per minute. Stroke volume is the volume of blood pumped per ventricular contraction.

For a typical resting adult human being at rest, CO is approximately 5 L/min.

CO = 70 contractions/min × 70 mL/contraction = 4,900 mL/min

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.

Refers to the concentration gradient of an ion or molecule. The concentration gradient may exist across a biological membrane, where the concentration is higher on one side of the membrane compared to the other side. Concentration gradient may also exist in a solution without an apparent barrier separating the area of higher concentration from the area of lower concentration. In both cases, the free energy that results from the concentration difference drives the movement of the ion/molcule from the area of higher concentration to the area of lower concentration. In free solution, the ion/molecule simply diffuses down its gradient. Movement across a biological membrane is more complicated and is a function of lipid solubility of the ion/molecule as well as the presence of channels or transport proteins that can allow the ion/molecule to cross the membrane (see Lipid Bilayer Permeability and Summary of Membrane Transport Processes).

Electrical gradient
Electrochemical gradient

A type of secondary active transport across a biological membrane in which a transport protein couples the movement of an ion (usually Na⁺ or H⁺) down its electrochemical gradient to the movement of another ion or molecule against a concentration or electrochemical gradient. The ion moving down its electrochemical gradient is referred to as the driving ion. The ion/molecule being transported against a chemical or electrochemical gradient is referred to as the driven ion/molecule.

In cotransport, the direction of transport is the same for both the driving ion and driven ion/molecule (into the cell or out of the cell).

An example is the Na⁺/glucose cotransporter (SGLT), which couples the movement of Na⁺ into the cell down its electrochemical gradient to the movement of glucose into the cell against its concentration gradient.

Cotransport is also commonly referred to as symport.

Transport proteins that are involved in this type of transport are referred to as cotransporters or symporters.

Symport

Secondary active transport
Exchange

Lecture notes on Secondary Active Transport

A potent blocker of nicotinic cholinergic receptors (nicotinic acetylcholine receptor, nAChR) found at the neuromuscular junction. At small doses, curare can lead to muscle weakness. At high doses, curare can lead to paralysis of skeletal muscles, which would also result in asphyxiation (and ultimately death) due to paralysis of the diaphragm. Curare was commonly the active agent of poison arrow.

See Wikipedia

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

The first region (i.e., most proximal region) of the small intestine. Chyme leaving the stomach (through the pyloric valve) first enters the duodenum. The contents of the duodenum empty into the jejunum (middle region of the small intestine). In adult humans, the duodenum is about 25-38 cm (10-15 inches) long.

Jejunum
Ileum

Difficult or painful intercourse.

ECG or EKG

A recording of the electrical activity of the heart measured by placing multiple (3 to 10) electrodes on the surface of the skin.

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).

Refers to the ability of some cells to be electrically excited resulting in the generation of action potentials. Neurons, muscle cells (skeletal, cardiac, and smooth), and some endocrine cells (e.g., insulin-releasing pancreatic β cells) are excitable cells.

Resting Membrane Potential - Introduction

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

Hyperthyroidism refers to a pathophysiological condition in which the thyroid gland produces and releases abnormally high levels of the thyroid hormones (T₃ and T₄).

The symptoms of hyperthyroidism may include high metabolic rate, weight loss, nervousness, excess heat production, tachycardia, and tremor.

Two main forms of hyperthyroidism exist: (1) Primary hyperthyroidism, and (2) Secondary hyperthyroidism.

In primary hyperthyroidism, the thyroid gland produces high levels of the thyroid hormones, either as a result of a secretory tumor of the thyroid gland, or under the control of thyroid stimulating immunoglobulins (such as in Graves' disease).

Secondary hypothyroidism is caused by high levels of thyroid stimulating hormone (TSH) produced by the anterior pituitary gland. TSH then stimulates the thyroid gland to produce excessive amounts of the thyroid hormones.

Hypothyroidism
Euthyroidism

The last region (i.e., most distal region) of the small intestine. Ileum receives the contents of the jejunum and, in turn, the contents of ileum leave the small intestine by emptying into the cecum. In adult humans, the ileum is about 2-4 meters (about 6.5-13 feet) long.

Duodenum
Jejunum

The middle region of the small intestine between the duodenum and the ileum. The jejunum receives the contents of the duodenum and, in turn, its contents empty into the ileum. In adult humans, the jejunum is about 2.5 meters (about 8 feet) long.

Duodenum
Ileum

The tapping sounds heard through a stethoscope placed over a partially compressed peripheral artery.

For the purpose of non-invasive blood pressure measurements, the stethoscope is usually placed on the skin overlying the brachial artery just distal to an inflated pressure cuff wrapped around the upper arm. As the pressure cuff is gradually deflated, the Korotkoff sounds result from the pulsations of the blood through the partially constricted brachial artery. With each ventricular systole, blood is forced to flow through the partially constricted brachial artery, and the turbulence in blood flow leads to the generation of the Korotkoff sounds. When the pressure cuff is fully deflated, flow through the artery resumes its normal laminar flow and, at that time, the Korotkoff sounds disappear.

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

A motor unit is composed of a motor neuron and all of the muscle fibers (i.e., muscle cells) it innervates.

Alternatively, a motor unit is a group of muscle fibers innervated by a single motor neuron.

A condition associated with hypothyroidism (especially primary hypothyroidism) in adults. It is characterized by thick, course skin, skin swelling (edema), and decreased metabolic rate and mental activity.

An equation used to calculate the equilibrium potential (V_eq.) of an ion. The equilibrium potential for an ion is also referred to as the Nernst potential for that ion. It is the membrane potential at which no net movement of the ion in question occurs across the membrane.



where V_eq. is the equilibrium potential, R is the universal gas constant, T is the temperature in Kelvin, z is the valence of the ionic species, F is the Faraday's constant, and [X]_o and [X]_i are the extracellular and intracellular, respectively, concentrations of the ion in question.

Resting Membrane Potential - Nernst Equilibrium Potential
Derivation of the Nernst Equation

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.

OAEs

Otoacoustic emissions (OAE) are sounds that arise from the organ of Corti within the cochlea of the inner ear in response to sound stimulation. They are thought to result from vibrations of cochlear outer hair cells (OHC) in response to stimulation by sound. Otoacoustic emissions are inaudible to the human ear, but can be recorded by placing a small recording device in the external auditory meatus (ear canal).

Otoacoustic emissions have clinical diagnostic value and are measured as part of hearing exams. In the newborn, otoacoustic emissions are recorded in order to detect blockage in the middle ear cavity (e.g., as a result of fluid accumulation) or external ear canal.

Physiology is the study of how living systems function. The scope of physiological studies ranges from the subcellular level (molecules and organelles) all the way to the level of the whole organism and how organisms adapt to vastly different environmental conditions such as hot, cold, dry, humid, or high altitude.

What is Physiology?

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

The condition of hearing a sound in the absence of an external sound stimulus. The sound may be ringing, buzzing, whistling, or hissing. The sound may be soft, loud, low-pitched, or high-pitched. It may be heard in one ear or both ears (simultaneously or independent of one another).

Tinnitus (Wikipedia)

Dry mouth. Dryness in the mouth resulting from abnormally low levels of saliva production.