Voltage-Gated Sodium Channel beta Subunits
Voltage-Gated Sodium Channel beta-1 Subunit
Sodium Channels
Voltage-Gated Sodium Channel beta-2 Subunit
Large-Conductance Calcium-Activated Potassium Channel beta Subunits
Voltage-Gated Sodium Channel beta-4 Subunit
Voltage-Gated Sodium Channel beta-3 Subunit
Protein Subunits
NAV1.2 Voltage-Gated Sodium Channel
Calcium Channels
Contactins
Ion Channel Gating
Sodium Channel Blockers
Molecular Sequence Data
Ion Channels
Sodium
Epithelial Sodium Channels
NAV1.5 Voltage-Gated Sodium Channel
NAV1.6 Voltage-Gated Sodium Channel
Cricetinae
Voltage-Gated Sodium Channels
Membrane Potentials
Electrophysiology
Patch-Clamp Techniques
Amino Acid Sequence
Calcium Channels, L-Type
Oocytes
NAV1.8 Voltage-Gated Sodium Channel
Sodium Channel Agonists
NAV1.1 Voltage-Gated Sodium Channel
NAV1.4 Voltage-Gated Sodium Channel
Xenopus
NAV1.7 Voltage-Gated Sodium Channel
Xenopus laevis
Calcium Channel Blockers
Potassium Channels, Inwardly Rectifying
Saxitoxin
Co-expression of Na(V)beta subunits alters the kinetics of inhibition of voltage-gated sodium channels by pore-blocking mu-conotoxins. (1/2)
(+info)Na+ channel-dependent recruitment of Navbeta4 to axon initial segments and nodes of Ranvier. (2/2)
(+info)Voltage-gated sodium channel beta subunits are regulatory proteins that accompany and modulate the function of voltage-gated sodium channels in excitable membranes, such as those found in nerve and muscle cells. These subunits are classified into four types (β1, β2, β3, and β4) and can be either transmembrane or glycosylphosphatidylinositol (GPI)-anchored proteins. They play crucial roles in modulating the biophysical properties of sodium channels, including channel expression, assembly, trafficking, and kinetics. The β subunits can also interact with other cell adhesion molecules to influence cell-cell interactions and signaling pathways. Overall, voltage-gated sodium channel beta subunits are essential for the proper functioning of electrical signaling in the nervous system and muscle tissue.
The voltage-gated sodium channel (Nav) beta-1 subunit, also known as SCN1B, is a regulatory protein that associates with the pore-forming alpha subunit of voltage-gated sodium channels. It is a transmembrane protein consisting of an extracellular domain, a single transmembrane segment, and a short intracellular domain.
The beta-1 subunit plays a crucial role in modulating the kinetic properties and expression levels of Nav channels. Specifically, it affects the activation, inactivation, and recovery from inactivation of sodium currents. The beta-1 subunit also functions as an adhesion molecule and interacts with extracellular matrix proteins, which helps to anchor Nav channels to the cytoskeleton and regulate their clustering at nodes of Ranvier in myelinated neurons.
Mutations in the SCN1B gene have been associated with various neurological disorders, including generalized epilepsy with febrile seizures plus (GEFS+), severe myoclonic epilepsy of infancy (SMEI), and Dravet syndrome, which is a severe form of childhood epilepsy. These mutations can affect the function and expression of Nav channels, leading to abnormal neuronal excitability and synchronization, and ultimately to seizures and other neurological symptoms.
Sodium channels are specialized protein structures that are embedded in the membranes of excitable cells, such as nerve and muscle cells. They play a crucial role in the generation and transmission of electrical signals in these cells. Sodium channels are responsible for the rapid influx of sodium ions into the cell during the initial phase of an action potential, which is the electrical signal that travels along the membrane of a neuron or muscle fiber. This sudden influx of sodium ions causes the membrane potential to rapidly reverse, leading to the depolarization of the cell. After the action potential, the sodium channels close and become inactivated, preventing further entry of sodium ions and helping to restore the resting membrane potential.
Sodium channels are composed of a large alpha subunit and one or two smaller beta subunits. The alpha subunit forms the ion-conducting pore, while the beta subunits play a role in modulating the function and stability of the channel. Mutations in sodium channel genes have been associated with various inherited diseases, including certain forms of epilepsy, cardiac arrhythmias, and muscle disorders.
The voltage-gated sodium channel β-2 subunit, also known as SCN3B or NaVβ2, is a regulatory protein that associates with the pore-forming α-subunit of voltage-gated sodium channels. These channels play crucial roles in generating and propagating action potentials in excitable cells such as neurons and muscle cells.
The β-2 subunit is a member of the immunoglobulin superfamily, containing an extracellular immunoglobulin-like domain, a transmembrane segment, and a short intracellular tail. The primary function of the β-2 subunit is to modulate the kinetic properties and plasma membrane expression of the sodium channel complex. It can influence the voltage dependence, activation, and inactivation of sodium currents, as well as the susceptibility to channel blockers.
The β-2 subunit also interacts with other cell adhesion molecules and extracellular matrix proteins, which may contribute to the proper localization and clustering of sodium channels at nodes of Ranvier in myelinated neurons or at the neuromuscular junction. Mutations in the SCN3B gene have been associated with various neurological disorders, including epilepsy and periodic paralyses.
Large-conductance calcium-activated potassium channels, also known as BK channels, are a type of ion channel that are activated by both voltage and increases in intracellular calcium concentrations. The pore-forming α subunit of the BK channel can be modulated by accessory β subunits, which are referred to as "large-conductance calcium-activated potassium channel beta subunits."
These β subunits are a family of proteins that consist of four members (β1-β4) and play a critical role in regulating the function of BK channels. They can modulate the activation kinetics, voltage dependence, and calcium sensitivity of the BK channel by binding to the α subunit.
The β subunits have distinct expression patterns and functions. For example, the β1 subunit is widely expressed in various tissues, including neurons, smooth muscle cells, and secretory cells, and it can slow down the activation kinetics of BK channels. The β2 subunit is predominantly expressed in neurons and can shift the voltage dependence of BK channel activation to more negative potentials. The β3 subunit is also primarily expressed in neurons and can reduce the calcium sensitivity of BK channels. Finally, the β4 subunit is mainly found in the brain and can inhibit BK channel activity.
Overall, large-conductance calcium-activated potassium channel beta subunits play a crucial role in regulating the function of BK channels, which are involved in various physiological processes, including neuronal excitability, muscle contraction, and hormone secretion.
The voltage-gated sodium channel β-4 subunit, also known as SCN4B, is a protein that forms part of the voltage-gated sodium channel complex in excitable cells such as neurons and muscle cells. The channel complex is responsible for the rapid influx of sodium ions into the cell during the initiation and propagation of action potentials.
The β-4 subunit is one of several accessory proteins that associate with the pore-forming α-subunit to modulate the function of the channel. Specifically, the β-4 subunit has been shown to regulate the kinetics and voltage dependence of sodium channel activation and inactivation, as well as the expression and trafficking of the channel complex to the cell membrane.
Mutations in the SCN4B gene, which encodes the β-4 subunit, have been associated with various forms of inherited peripheral nerve hyperexcitability disorders, such as paramyotonia congenita and hyperkalemic periodic paralysis. These disorders are characterized by muscle stiffness, cramping, and weakness in response to cold or exercise, and are thought to result from abnormalities in sodium channel function.
The voltage-gated sodium channel β-3 subunit, also known as SCN3B or NaVβ4, is a regulatory protein that associates with the pore-forming α-subunit of voltage-gated sodium channels. This subunit is encoded by the SCN3B gene in humans.
The β-3 subunit is a member of the immunoglobulin superfamily and contains an extracellular immunoglobulin domain, a transmembrane region, and a short intracellular tail. It plays a role in modulating the biophysical properties and expression levels of sodium channels, which are crucial for the initiation and propagation of action potentials in excitable cells such as neurons and cardiomyocytes.
Mutations in the SCN3B gene have been associated with various neurological disorders, including epilepsy and developmental delay. Proper functioning of voltage-gated sodium channels is essential for normal nervous system function, and disruptions to these channels can lead to a range of clinical manifestations.
A protein subunit refers to a distinct and independently folding polypeptide chain that makes up a larger protein complex. Proteins are often composed of multiple subunits, which can be identical or different, that come together to form the functional unit of the protein. These subunits can interact with each other through non-covalent interactions such as hydrogen bonds, ionic bonds, and van der Waals forces, as well as covalent bonds like disulfide bridges. The arrangement and interaction of these subunits contribute to the overall structure and function of the protein.
NAV1.2, also known as SCN2A, is a type of voltage-gated sodium channel that is primarily expressed in the central nervous system, including the brain and spinal cord. Voltage-gated sodium channels are transmembrane proteins that play a crucial role in the generation and propagation of action potentials in excitable cells such as neurons.
NAV1.2 voltage-gated sodium channels are responsible for the initiation and early phase of action potentials in neurons. They are activated by depolarization of the membrane potential and allow the influx of sodium ions into the cell, which leads to a rapid depolarization of the membrane. This triggers the opening of additional voltage-gated sodium channels, leading to a regenerative response that results in the generation of an action potential.
Mutations in the SCN2A gene, which encodes the NAV1.2 channel, have been associated with various neurological disorders, including epilepsy, autism spectrum disorder, and intellectual disability. These mutations can alter the function of the NAV1.2 channel, leading to changes in neuronal excitability and network activity that contribute to the development of these disorders.
Calcium channels are specialized proteins that span the membrane of cells and allow calcium ions (Ca²+) to flow in and out of the cell. They are crucial for many physiological processes, including muscle contraction, neurotransmitter release, hormone secretion, and gene expression.
There are several types of calcium channels, classified based on their biophysical and pharmacological properties. The most well-known are:
1. Voltage-gated calcium channels (VGCCs): These channels are activated by changes in the membrane potential. They are further divided into several subtypes, including L-type, P/Q-type, N-type, R-type, and T-type. VGCCs play a critical role in excitation-contraction coupling in muscle cells and neurotransmitter release in neurons.
2. Receptor-operated calcium channels (ROCCs): These channels are activated by the binding of an extracellular ligand, such as a hormone or neurotransmitter, to a specific receptor on the cell surface. ROCCs are involved in various physiological processes, including smooth muscle contraction and platelet activation.
3. Store-operated calcium channels (SOCCs): These channels are activated by the depletion of intracellular calcium stores, such as those found in the endoplasmic reticulum. SOCCs play a critical role in maintaining calcium homeostasis and signaling within cells.
Dysregulation of calcium channel function has been implicated in various diseases, including hypertension, arrhythmias, migraine, epilepsy, and neurodegenerative disorders. Therefore, calcium channels are an important target for drug development and therapy.
Contactins are a family of glycosylphosphatidylinositol (GPI)-anchored neuronal cell adhesion molecules that play important roles in the nervous system. They are involved in the formation and maintenance of neural connections, including axon guidance, fasciculation, and synaptogenesis. Contactins have immunoglobulin-like domains and fibronectin type III repeats, which mediate their homophilic or heterophilic interactions with other molecules on the cell surface. There are six known members of the contactin family: contactin-1 (also known as F3), contactin-2 (TAG-1), contactin-3 (BIG-1), contactin-4 (BIG-2), contactin-5, and contactin-6. Mutations in some contactin genes have been associated with neurological disorders such as X-linked mental retardation and epilepsy.
Ion channel gating refers to the process by which ion channels in cell membranes open and close in response to various stimuli, allowing ions such as sodium, potassium, and calcium to flow into or out of the cell. This movement of ions is crucial for many physiological processes, including the generation and transmission of electrical signals in nerve cells, muscle contraction, and the regulation of hormone secretion.
Ion channel gating can be regulated by various factors, including voltage changes across the membrane (voltage-gated channels), ligand binding (ligand-gated channels), mechanical stress (mechanosensitive channels), or other intracellular signals (second messenger-gated channels). The opening and closing of ion channels are highly regulated and coordinated processes that play a critical role in maintaining the proper functioning of cells and organ systems.
Sodium channel blockers are a class of medications that work by blocking sodium channels in the heart, which prevents the rapid influx of sodium ions into the cells during depolarization. This action slows down the rate of impulse generation and propagation in the heart, which in turn decreases the heart rate and prolongs the refractory period.
Sodium channel blockers are primarily used to treat cardiac arrhythmias, including atrial fibrillation, atrial flutter, and ventricular tachycardia. They may also be used to treat certain types of neuropathic pain. Examples of sodium channel blockers include Class I antiarrhythmics such as flecainide, propafenone, lidocaine, and mexiletine.
It's important to note that sodium channel blockers can have potential side effects, including proarrhythmia (i.e., the development of new arrhythmias or worsening of existing ones), negative inotropy (decreased contractility of the heart muscle), and cardiac conduction abnormalities. Therefore, these medications should be used with caution and under the close supervision of a healthcare provider.
Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.
Ion channels are specialized transmembrane proteins that form hydrophilic pores or gaps in the lipid bilayer of cell membranes. They regulate the movement of ions (such as sodium, potassium, calcium, and chloride) across the cell membrane by allowing these charged particles to pass through selectively in response to various stimuli, including voltage changes, ligand binding, mechanical stress, or temperature changes. This ion movement is essential for many physiological processes, including electrical signaling, neurotransmission, muscle contraction, and maintenance of resting membrane potential. Ion channels can be categorized based on their activation mechanisms, ion selectivity, and structural features. Dysfunction of ion channels can lead to various diseases, making them important targets for drug development.
Sodium is an essential mineral and electrolyte that is necessary for human health. In a medical context, sodium is often discussed in terms of its concentration in the blood, as measured by serum sodium levels. The normal range for serum sodium is typically between 135 and 145 milliequivalents per liter (mEq/L).
Sodium plays a number of important roles in the body, including:
* Regulating fluid balance: Sodium helps to regulate the amount of water in and around your cells, which is important for maintaining normal blood pressure and preventing dehydration.
* Facilitating nerve impulse transmission: Sodium is involved in the generation and transmission of electrical signals in the nervous system, which is necessary for proper muscle function and coordination.
* Assisting with muscle contraction: Sodium helps to regulate muscle contractions by interacting with other minerals such as calcium and potassium.
Low sodium levels (hyponatremia) can cause symptoms such as confusion, seizures, and coma, while high sodium levels (hypernatremia) can lead to symptoms such as weakness, muscle cramps, and seizures. Both conditions require medical treatment to correct.
Epithelial Sodium Channels (ENaC) are a type of ion channel found in the epithelial cells that line the surface of many types of tissues, including the airways, kidneys, and colon. These channels play a crucial role in regulating sodium and fluid balance in the body by allowing the passive movement of sodium ions (Na+) from the lumen or outside of the cell to the inside of the cell, following their electrochemical gradient.
ENaC is composed of three subunits, alpha, beta, and gamma, which are encoded by different genes. The channel is normally closed and opens in response to various stimuli, such as hormones, neurotransmitters, or changes in osmolarity. Once open, the channel allows sodium ions to flow through, creating a positive charge that can attract chloride ions (Cl-) and water molecules, leading to fluid absorption.
In the kidneys, ENaC plays an essential role in regulating sodium reabsorption in the distal nephron, which helps maintain blood pressure and volume. In the airways, ENaC is involved in controlling the hydration of the airway surface liquid, which is necessary for normal mucociliary clearance. Dysregulation of ENaC has been implicated in several diseases, including hypertension, cystic fibrosis, and chronic obstructive pulmonary disease (COPD).
NAV1.5, also known as SCN5A, is a specific type of voltage-gated sodium channel found in the heart muscle cells (cardiomyocytes). These channels play a crucial role in the generation and transmission of electrical signals that coordinate the contraction of the heart.
More specifically, NAV1.5 channels are responsible for the rapid influx of sodium ions into cardiomyocytes during the initial phase of the action potential, which is the electrical excitation of the cell. This rapid influx of sodium ions helps to initiate and propagate the action potential throughout the heart muscle, allowing for coordinated contraction and proper heart function.
Mutations in the SCN5A gene, which encodes the NAV1.5 channel, have been associated with various cardiac arrhythmias, including long QT syndrome, Brugada syndrome, and familial atrial fibrillation, among others. These genetic disorders can lead to abnormal heart rhythms, syncope, and in some cases, sudden cardiac death.
NAV1.6, also known as SCN8A, is a gene that encodes for the α subunit of a voltage-gated sodium channel, specifically Nav1.6. This channel plays a crucial role in the initiation and propagation of action potentials in neurons. It has a predominant expression in the central and peripheral nervous system, including the nodes of Ranvier in myelinated axons.
Nav1.6 voltage-gated sodium channels are responsible for the rapid upstroke of the action potential and contribute to the generation of repetitive firing in some neuronal populations. Mutations in the SCN8A gene have been associated with various neurological disorders, such as epilepsy, intellectual disability, and movement disorders.
In summary, NAV1.6 voltage-gated sodium channels are essential for normal neuronal excitability and function, and their dysfunction can lead to a range of neurological symptoms.
Cricetinae is a subfamily of rodents that includes hamsters, gerbils, and relatives. These small mammals are characterized by having short limbs, compact bodies, and cheek pouches for storing food. They are native to various parts of the world, particularly in Europe, Asia, and Africa. Some species are popular pets due to their small size, easy care, and friendly nature. In a medical context, understanding the biology and behavior of Cricetinae species can be important for individuals who keep them as pets or for researchers studying their physiology.
Voltage-gated sodium channels are specialized protein complexes found in the membranes of excitable cells, such as neurons and muscle cells. They play a crucial role in the generation and propagation of action potentials, which are the electrical signals that allow these cells to communicate and coordinate their activities.
Structurally, voltage-gated sodium channels consist of a large alpha subunit that forms the ion-conducting pore, as well as one or more beta subunits that modulate the channel's properties. The alpha subunit contains four repeating domains (I-IV), each of which contains six transmembrane segments (S1-S6).
The channel is closed at resting membrane potentials but can be activated by depolarization of the membrane, leading to the opening of the pore and the rapid influx of sodium ions into the cell. This influx of positive charges further depolarizes the membrane, leading to the activation of additional voltage-gated sodium channels and the propagation of the action potential along the cell membrane.
Voltage-gated sodium channels are critical for normal physiological processes such as nerve impulse transmission and muscle contraction. However, mutations in these channels can lead to a variety of channelopathies, including inherited neurological disorders such as epilepsy and peripheral neuropathy. Additionally, certain drugs and toxins can target voltage-gated sodium channels, leading to altered electrical activity in excitable cells and potential toxicity or therapeutic effects.
Membrane potential is the electrical potential difference across a cell membrane, typically for excitable cells such as nerve and muscle cells. It is the difference in electric charge between the inside and outside of a cell, created by the selective permeability of the cell membrane to different ions. The resting membrane potential of a typical animal cell is around -70 mV, with the interior being negative relative to the exterior. This potential is generated and maintained by the active transport of ions across the membrane, primarily through the action of the sodium-potassium pump. Membrane potentials play a crucial role in many physiological processes, including the transmission of nerve impulses and the contraction of muscle cells.
Electrophysiology is a branch of medicine that deals with the electrical activities of the body, particularly the heart. In a medical context, electrophysiology studies (EPS) are performed to assess abnormal heart rhythms (arrhythmias) and to evaluate the effectiveness of certain treatments, such as medication or pacemakers.
During an EPS, electrode catheters are inserted into the heart through blood vessels in the groin or neck. These catheters can record the electrical activity of the heart and stimulate it to help identify the source of the arrhythmia. The information gathered during the study can help doctors determine the best course of treatment for each patient.
In addition to cardiac electrophysiology, there are also other subspecialties within electrophysiology, such as neuromuscular electrophysiology, which deals with the electrical activity of the nervous system and muscles.
Patch-clamp techniques are a group of electrophysiological methods used to study ion channels and other electrical properties of cells. These techniques were developed by Erwin Neher and Bert Sakmann, who were awarded the Nobel Prize in Physiology or Medicine in 1991 for their work. The basic principle of patch-clamp techniques involves creating a high resistance seal between a glass micropipette and the cell membrane, allowing for the measurement of current flowing through individual ion channels or groups of channels.
There are several different configurations of patch-clamp techniques, including:
1. Cell-attached configuration: In this configuration, the micropipette is attached to the outer surface of the cell membrane, and the current flowing across a single ion channel can be measured. This configuration allows for the study of the properties of individual channels in their native environment.
2. Whole-cell configuration: Here, the micropipette breaks through the cell membrane, creating a low resistance electrical connection between the pipette and the inside of the cell. This configuration allows for the measurement of the total current flowing across all ion channels in the cell membrane.
3. Inside-out configuration: In this configuration, the micropipette is pulled away from the cell after establishing a seal, resulting in the exposure of the inner surface of the cell membrane to the solution in the pipette. This configuration allows for the study of the properties of ion channels in isolation from other cellular components.
4. Outside-out configuration: Here, the micropipette is pulled away from the cell after establishing a seal, resulting in the exposure of the outer surface of the cell membrane to the solution in the pipette. This configuration allows for the study of the properties of ion channels in their native environment, but with the ability to control the composition of the extracellular solution.
Patch-clamp techniques have been instrumental in advancing our understanding of ion channel function and have contributed to numerous breakthroughs in neuroscience, pharmacology, and physiology.
An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.
Calcium channels, L-type, are a type of voltage-gated calcium channel that are widely expressed in many excitable cells, including cardiac and skeletal muscle cells, as well as certain neurons. These channels play a crucial role in the regulation of various cellular functions, such as excitation-contraction coupling, hormone secretion, and gene expression.
L-type calcium channels are composed of five subunits: alpha-1, alpha-2, beta, gamma, and delta. The alpha-1 subunit is the pore-forming subunit that contains the voltage sensor and the selectivity filter for calcium ions. It has four repeated domains (I-IV), each containing six transmembrane segments (S1-S6). The S4 segment in each domain functions as a voltage sensor, moving outward upon membrane depolarization to open the channel and allow calcium ions to flow into the cell.
L-type calcium channels are activated by membrane depolarization and have a relatively slow activation and inactivation time course. They are also modulated by various intracellular signaling molecules, such as protein kinases and G proteins. L-type calcium channel blockers, such as nifedipine and verapamil, are commonly used in the treatment of hypertension, angina, and certain cardiac arrhythmias.
An oocyte, also known as an egg cell or female gamete, is a large specialized cell found in the ovary of female organisms. It contains half the number of chromosomes as a normal diploid cell, as it is the product of meiotic division. Oocytes are surrounded by follicle cells and are responsible for the production of female offspring upon fertilization with sperm. The term "oocyte" specifically refers to the immature egg cell before it reaches full maturity and is ready for fertilization, at which point it is referred to as an ovum or egg.
NAV1.8 (SCN10A) voltage-gated sodium channel is a type of ion channel found in excitable cells such as neurons and some types of immune cells. These channels play a crucial role in the generation and transmission of electrical signals in the form of action potentials. The NAV1.8 subtype, specifically, is primarily expressed in peripheral nervous system tissues, including sensory neurons responsible for pain perception.
NAV1.8 voltage-gated sodium channels are composed of four homologous domains (I-IV), each containing six transmembrane segments (S1-S6). The S4 segment in each domain functions as a voltage sensor, moving in response to changes in the membrane potential. When the membrane potential becomes more positive (depolarized), the S4 segment moves outward, which opens the channel and allows sodium ions (Na+) to flow into the cell. This influx of Na+ ions further depolarizes the membrane, leading to the rapid upstroke of the action potential.
The NAV1.8 channels are known for their unique biophysical properties, including slow activation and inactivation kinetics, as well as relative resistance to tetrodotoxin (TTX), a neurotoxin that blocks most voltage-gated sodium channels. These characteristics make NAV1.8 channels particularly important for generating and maintaining the electrical excitability of nociceptive neurons, which are responsible for transmitting pain signals from the periphery to the central nervous system.
Mutations in the SCN10A gene, which encodes the NAV1.8 channel, have been associated with various pain-related disorders, such as inherited erythromelalgia and small fiber neuropathies, highlighting their significance in pain physiology and pathophysiology.
Sodium channel agonists are substances that enhance the activity or function of sodium channels. Sodium channels are membrane proteins that play a crucial role in the generation and transmission of electrical signals in excitable cells, such as nerve and muscle cells. They allow the influx of sodium ions into the cell, which leads to the depolarization of the cell membrane and the initiation of an action potential.
Sodium channel agonists increase the likelihood, duration, or amplitude of action potentials by promoting the opening of sodium channels or slowing their closure. These effects can have various physiological consequences depending on the type of cell and tissue involved. In some cases, sodium channel agonists may be used for therapeutic purposes, such as in the treatment of certain types of heart arrhythmias. However, they can also have harmful or toxic effects, especially when used in excessive amounts or in sensitive populations.
Examples of sodium channel agonists include some drugs used to treat cardiac arrhythmias, such as Class I antiarrhythmic agents like ajmaline, flecainide, and procainamide. These drugs bind to the sodium channels and stabilize their open state, reducing the frequency and velocity of action potentials in the heart. Other substances that can act as sodium channel agonists include certain neurotoxins, such as batrachotoxin and veratridine, which are found in some species of plants and animals and can have potent effects on nerve and muscle function.
NAV1.1, also known as SCN1A, is a type of voltage-gated sodium channel that is primarily expressed in the central nervous system, including the brain and spinal cord. Voltage-gated sodium channels are transmembrane proteins that play a crucial role in the generation and propagation of action potentials in excitable cells such as neurons.
NAV1.1 voltage-gated sodium channels are responsible for the initiation and propagation of action potentials in the axons of neurons. They are composed of a large alpha subunit, which forms the ion conduction pore, and one or more beta subunits, which modulate the properties of the channel.
Mutations in the SCN1A gene, which encodes the NAV1.1 voltage-gated sodium channel, have been associated with several neurological disorders, including generalized epilepsy with febrile seizures plus (GEFS+), Dravet syndrome, and other forms of epilepsy. These mutations can alter the function of the channel, leading to abnormal neuronal excitability and seizure activity.
NAV1.4, also known as SCN4A, is a gene that encodes for the α subunit of the voltage-gated sodium channel in humans. This channel, specifically located in the skeletal muscle, is responsible for the rapid influx of sodium ions during the initiation and propagation of action potentials, which are critical for muscle contraction.
The NAV1.4 Voltage-Gated Sodium Channel plays a crucial role in the functioning of skeletal muscles. Mutations in this gene can lead to various neuromuscular disorders such as hyperkalemic periodic paralysis, paramyotonia congenita, and potassium-aggravated myotonia, which are characterized by muscle stiffness, cramps, and episodes of weakness or paralysis.
"Xenopus" is not a medical term, but it is a genus of highly invasive aquatic frogs native to sub-Saharan Africa. They are often used in scientific research, particularly in developmental biology and genetics. The most commonly studied species is Xenopus laevis, also known as the African clawed frog.
In a medical context, Xenopus might be mentioned when discussing their use in research or as a model organism to study various biological processes or diseases.
NAV1.7, also known as SCN9A, is a gene that encodes for the α subunit of a voltage-gated sodium channel. This specific sodium channel, referred to as the Nav1.7 voltage-gated sodium channel, plays a crucial role in the initiation and propagation of action potentials in neurons, particularly in peripheral nerves.
The Nav1.7 channel is primarily responsible for generating the rapid upstroke of the action potential, which is essential for nerve impulse transmission. It exhibits unique biophysical properties, such as slow activation, fast inactivation, and rapid repriming, making it highly sensitive to small changes in membrane voltage. This sensitivity allows Nav1.7 channels to function as threshold channels, selectively amplifying subthreshold depolarizations and contributing to the generation of action potentials.
Dysfunction in the Nav1.7 channel has been implicated in various pain-related disorders. Gain-of-function mutations in the SCN9A gene can lead to chronic pain conditions, such as inherited erythromelalgia and paroxysmal extreme pain disorder. In contrast, loss-of-function mutations have been associated with congenital insensitivity to pain, a rare condition characterized by the inability to experience pain. Thus, Nav1.7 channels are considered promising targets for the development of novel analgesic drugs.
"Xenopus laevis" is not a medical term itself, but it refers to a specific species of African clawed frog that is often used in scientific research, including biomedical and developmental studies. Therefore, its relevance to medicine comes from its role as a model organism in laboratories.
In a broader sense, Xenopus laevis has contributed significantly to various medical discoveries, such as the understanding of embryonic development, cell cycle regulation, and genetic research. For instance, the Nobel Prize in Physiology or Medicine was awarded in 1963 to John R. B. Gurdon and Sir Michael J. Bishop for their discoveries concerning the genetic mechanisms of organism development using Xenopus laevis as a model system.
Electric conductivity, also known as electrical conductance, is a measure of a material's ability to allow the flow of electric current through it. It is usually measured in units of Siemens per meter (S/m) or ohm-meters (Ω-m).
In medical terms, electric conductivity can refer to the body's ability to conduct electrical signals, which is important for various physiological processes such as nerve impulse transmission and muscle contraction. Abnormalities in electrical conductivity can be associated with various medical conditions, including neurological disorders and heart diseases.
For example, in electrocardiography (ECG), the electric conductivity of the heart is measured to assess its electrical activity and identify any abnormalities that may indicate heart disease. Similarly, in electromyography (EMG), the electric conductivity of muscles is measured to diagnose neuromuscular disorders.
Calcium channel blockers (CCBs) are a class of medications that work by inhibiting the influx of calcium ions into cardiac and smooth muscle cells. This action leads to relaxation of the muscles, particularly in the blood vessels, resulting in decreased peripheral resistance and reduced blood pressure. Calcium channel blockers also have anti-arrhythmic effects and are used in the management of various cardiovascular conditions such as hypertension, angina, and certain types of arrhythmias.
Calcium channel blockers can be further classified into two main categories based on their chemical structure: dihydropyridines (e.g., nifedipine, amlodipine) and non-dihydropyridines (e.g., verapamil, diltiazem). Dihydropyridines are more selective for vascular smooth muscle and have a greater effect on blood pressure than heart rate or conduction. Non-dihydropyridines have a more significant impact on cardiac conduction and contractility, in addition to their vasodilatory effects.
It is important to note that calcium channel blockers may interact with other medications and should be used under the guidance of a healthcare professional. Potential side effects include dizziness, headache, constipation, and peripheral edema.
Inwardly rectifying potassium channels (Kir) are a type of potassium channel that allow for the selective passage of potassium ions (K+) across cell membranes. The term "inwardly rectifying" refers to their unique property of allowing potassium ions to flow more easily into the cell (inward current) than out of the cell (outward current). This characteristic is due to the voltage-dependent blockage of these channels by intracellular magnesium and polyamines at depolarized potentials.
These channels play crucial roles in various physiological processes, including:
1. Resting membrane potential maintenance: Kir channels help establish and maintain the negative resting membrane potential in cells by facilitating potassium efflux when the membrane potential is near the potassium equilibrium potential (Ek).
2. Action potential repolarization: In excitable cells like neurons and muscle fibers, Kir channels contribute to the rapid repolarization phase of action potentials, allowing for proper electrical signaling.
3. Cell volume regulation: Kir channels are involved in regulating cell volume by mediating potassium influx during osmotic stress or changes in intracellular ion concentrations.
4. Insulin secretion: In pancreatic β-cells, Kir channels control the membrane potential and calcium signaling necessary for insulin release.
5. Renal function: Kir channels are essential for maintaining electrolyte balance and controlling renal tubular transport in the kidneys.
There are several subfamilies of inwardly rectifying potassium channels (Kir1-7), each with distinct biophysical properties, tissue distributions, and functions. Mutations in genes encoding these channels can lead to various human diseases, including cardiac arrhythmias, epilepsy, and Bartter syndrome.
Saxitoxin (STX) is a potent neurotoxin that inhibits the sodium channels in nerve cells, leading to paralysis and potentially death. It is produced by certain species of marine dinoflagellates and cyanobacteria, and can accumulate in shellfish that feed on these organisms. Saxitoxin poisoning, also known as paralytic shellfish poisoning (PSP), is a serious medical condition that can cause symptoms such as numbness, tingling, and paralysis of the mouth and extremities, as well as respiratory failure and death in severe cases. It is important to note that saxitoxin is not used as a therapeutic agent in medicine and is considered a harmful substance.
In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."
1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.
2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.
3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.
4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).
Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.
SCN2B
SCN1B
SCN3B
SCN3A
Nav1.4
SCN1A
Nav1.9
SCN2A
Romano-Ward syndrome
Sodium channel
Cardiac action potential
Raventoxin
Long QT syndrome
SCN4B
Dendritic spike
SCNN1B
SCNN1G
Acetylcholine receptor
Voltage-gated ion channel
DKK-Sp1
Scorpion toxin
Voltage-gated potassium channel
Neosaxitoxin
Generalized epilepsy with febrile seizures plus
Voltage-gated calcium channel
AsKC11
Plakophilin-2
KCNE5
Chromosome 3
Protoxin-I
Orphanet: sodium voltage gated channel beta subunit 4
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Composed of a large alpha subunit1
- Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. (nih.gov)
Action potentials7
- Voltage-gated sodium channels (NaV) are essential for the generation of action potentials and for cell excitability. (thermofisher.com)
- Voltage-gated sodium channels function in the generation and propagation of action potentials in neurons and muscle. (nih.gov)
- Voltage-gated sodium channels mediate a rapid and transient increase in Na + permeability in response to membrane depolarization, thereby contributing to the generation and conduction of action potentials. (jneurosci.org)
- The Swarm was able to record pseudo-action potentials stably across all 24 objectives and provided pharmacological characterization of diverse sodium channel blockers. (frontiersin.org)
- The sodium current underlying action potentials in guinea pig hippocampal CA1 neurons. (xenbase.org)
- Voltage-sensitive ion channels closely regulate generation of action potentials (brief and reversible alterations of the voltage of cellular membranes). (medscape.com)
- During the generation of action potentials, sodium ions move across the membrane through voltage-gated ion channels. (medscape.com)
Mutations14
- Sodium channel SCN1A and epilepsy: mutations and mechanisms. (springer.com)
- Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. (springer.com)
- SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. (springer.com)
- FEPS2 is an autosomal dominant neurologic disorder caused by heterozygous missense mutations involving the voltage-gated sodium channel type X, alpha subunit ( SCN10A ) gene (Faber et al. (preventiongenetics.com)
- Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI) can be due to the mutations in the same residue of the alpha-subunit of a voltage gated sodium channel encoded by SCN1A. (epilepsygenetics.net)
- Some sodium channel isoforms that are not expressed normally in the adult cerebellum are expressed in animals with mutations or disease. (nih.gov)
- Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita. (xenbase.org)
- Changes in sodium channel gating produced by point mutations in a cytoplasmic linker. (xenbase.org)
- Advances in molecular diagnostics have revealed that Bartter syndrome results from mutations in numerous genes that affect the function of ion channels and transporters that normally mediate transepithelial salt reabsorption in the distal nephron segments (see the image below). (medscape.com)
- Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment. (bvsalud.org)
- With HyperPP fast channel inactivation, mutations are usually situated in the inner parts of transmembrane segments or in the intracellular loops affecting the docking sites for the fast inactivating particle, thus impairing fast channel inactivation leading to persistent Na + current. (medscape.com)
- Genetic etiology of PE is mutations on SCN9A , the encoding gene of a voltage-gated sodium channel subtype Nav1.7. (biomedcentral.com)
- This review mainly focuses on PE and the causative gene SCN9A -- its mutations and their effects on Nav1.7 channels' electrophysiological properties. (biomedcentral.com)
- PE is exclusively caused by mutations in SCN9A , the encoding gene of sodium channel subtype Nav1.7 and can be sub-classified into familial (inherited erythromelalgia) and sporadic forms. (biomedcentral.com)
Ions8
- NaV channels are activated in response to depolarization and selectively allow flow of Na+ ions. (thermofisher.com)
- Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. (nih.gov)
- This negative potential is created by energy-dependent outward transport of sodium and inward transport of potassium ions, combined with greater membrane permeability to potassium ions relative to sodium ions. (aneskey.com)
- With excitation of the nerve, there is an increase in the membrane permeability to sodium ions, causing a decrease in the transmembrane potential. (aneskey.com)
- If a critical potential is reached (i.e., threshold potential), there is a rapid and self-sustaining influx of sodium ions resulting in a propagating wave of depolarization, the action potential, after which the resting membrane potential is reestablished. (aneskey.com)
- Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo. (xenbase.org)
- Background The epithelial sodium channel (ENaC) is a membrane-bound ion-channel that is selectively permeable to Na+ ions and that is assembled as a heterotrimer composed of three homologous subunits alpha, beta, and g. (qedbio.com)
- It is involved primarily in the reabsorption of sodium ions in the collecting ducts of the kidney's nephrons. (qedbio.com)
SCN2B3
- Sodium channel subunit beta-2 is a protein that in humans is encoded by the SCN2B gene. (wikipedia.org)
- SCN2B+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Overview of all the structural information available in the PDB for UniProt: O60939 (Sodium channel subunit beta-2) at the PDBe-KB. (wikipedia.org)
- Sodium channel subunit beta-2 or Navbeta2 Na+ channel is encoded by SCN2B. (antibodiesinc.com)
Alpha13
- 1. We have compared the mRNA distribution of sodium channel alpha subunits known to be expressed during development with the known auxiliary subunits Na beta1.1 and Na beta2.1 and the novel, recently cloned subunit, beta3. (warwick.ac.uk)
- They form a heterotrimeric complex with the pore-forming sodium channel alpha subunits. (nih.gov)
- To date, nine NaV alpha subunits have been cloned and named NaV1.1-NaV1.9. (thermofisher.com)
- Mammalian sodium channels are heterotrimers, composed of a central, pore-forming alpha subunit and two auxiliary beta subunits. (thermofisher.com)
- The expression of the alpha subunit isoform is developmentally regulated and tissue specific. (thermofisher.com)
- Voltage gated sodium channels are made up of an alpha (pore forming) subunit and 1 or 2 beta subunits. (antibodiesinc.com)
- It non-covalently associates with voltage-gated alpha subunits. (nih.gov)
- This gene encodes one member of the sodium channel alpha subunit gene family. (nih.gov)
- Sodium channels are heteromultimeric membrane proteins, consisting of a large alpha subunit that forms the pore, and one or more beta subunits. (nih.gov)
- Ten genes encode an alpha subunit in mammals, and of these, four are expressed in the cerebellum: Nav1.1, Nav1.2, Nav1.3 and Nav1.6. (nih.gov)
- A rat brain Na+ channel alpha subunit with novel gating properties. (xenbase.org)
- Defects in the SCN9A gene, which codes for the alpha subunit of this sodium channel, are associated with several pain sensation-related disorders. (ucdenver.edu)
- Defects in the SCN2A gene which codes for the alpha subunit of this sodium channel are associated with benign familial infantile seizures type 3, and early infantile epileptic encephalopathy type 11. (rush.edu)
Protein4
- Navß2 is a transmembrane protein and acts as a regulatory subunit in excitable membranes and modulates the kinetics of channel. (antibodiesinc.com)
- Thus, most of the expression studies have relied on techniques that allow visualization of sodium channel subtypes at the level of mRNA and protein. (nih.gov)
- Functional modulation of brain sodium channels by protein kinase C phosphorylation. (xenbase.org)
- Description Western Blot analysis of Mouse Whole kidney homogenates showing detection of ~87kDa ENaC beta protein using Mouse Anti-ENaC beta Monoclonal Antibody, Clone 7B8 (11577). (qedbio.com)
Nav1.34
- 4. Emulsion-dipped slides showed co-localisation of beta3 with Nav1.3 mRNA in areas of the CNS suggesting that these subunits may be capable of functional interaction. (warwick.ac.uk)
- beta3 changed the equilibrium of Nav1.3 between the fast, and slow gating modes and caused a negative shift in the voltage dependence of activation and inactivation. (warwick.ac.uk)
- 6. In conclusion, beta3 is shown to be the predominant beta subunit expressed during development and is capable of modulating the kinetic properties of the embryonic Nav1.3 subunit. (warwick.ac.uk)
- The NaV channels are classified into two groups according to their sensitivity to tetrodotoxin (TTX): TTX-sensitive (NaV1.1, NaV1.2, NaV1.3, NaV1.4, NaV1.6 and NaV1.7) and TTX-resistant (NaV1.5, NaV1.8 and NaV1.9). (thermofisher.com)
SCN9A1
- The causative gene for PE, SCN9A , encodes a voltage-gated sodium channel (VGSC) subtype Nav1.7. (biomedcentral.com)
Nav1.77
- The voltage-gated Na + channel subtype Nav1.7 is important for pain and itch in rodents and humans. (springer.com)
- ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. (springer.com)
- To evaluate the Swarm screening system, we optimized a series of heterologous optogenetic spiking HEK293 cell assays for several voltage-gated sodium channel subtypes including Nav1.2, Nav1.5, and Nav1.7. (frontiersin.org)
- NAV1.7 Voltage-Gated Sodium Channel" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (ucdenver.edu)
- This graph shows the total number of publications written about "NAV1.7 Voltage-Gated Sodium Channel" by people in this website by year, and whether "NAV1.7 Voltage-Gated Sodium Channel" was a major or minor topic of these publications. (ucdenver.edu)
- Below are the most recent publications written about "NAV1.7 Voltage-Gated Sodium Channel" by people in Profiles. (ucdenver.edu)
- Wang ZJ, Tabakoff B, Levinson SR, Heinbockel T. Inhibition of Nav1.7 channels by methyl eugenol as a mechanism underlying its antinociceptive and anesthetic actions. (ucdenver.edu)
Subtype2
- A voltage-gated sodium channel subtype found widely expressed in nociceptive primary sensory neurons. (ucdenver.edu)
- A voltage-gated sodium channel subtype that mediates the sodium ion permeability of excitable membranes. (rush.edu)
Excitable2
- Mediates the voltage-dependent sodium ion permeability of excitable membranes. (nih.gov)
- To address this challenge, we developed the Swarm TM , a custom designed optical instrument for highly parallelized, multicolor measurements in excitable cells, simultaneously recording changes in voltage and calcium activities at high temporal resolution under optical stimulation. (frontiersin.org)
Skeletal2
- Jurkat-Rott K, Holzherr B, Fauler M, Lehmann-Horn F. Sodium channelopathies of skeletal muscle result from gain or loss of function. (springer.com)
- Sodium channels in the adult central nervous system and heart contain beta 1 through beta 4 subunits, whereas sodium channels in adult skeletal muscle have only the beta 1 subunit. (thermofisher.com)
Calcium3
- Structure and function of voltage-gated sodium and calcium channels. (xenbase.org)
- Sodium channelopathies are better understood than calcium or chloride channelopathies. (medscape.com)
- Discussion in this article primarily addresses the sodium, calcium, and potassium channelopathies as well as secondary forms of PP. Chloride channelopathies are not associated with episodic weakness and are discussed in more detail in the articles on myotonic disorders. (medscape.com)
Functional4
- Voltage-gated sodium channel subunits that play a role in the assembly, expression, and functional modulation of the sodium channel. (nih.gov)
- Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. (xenbase.org)
- Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. (bvsalud.org)
- Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. (bvsalud.org)
Epithelial1
- Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. (qedbio.com)
Activation and inactivation1
- Structural parts involved in activation and inactivation of the sodium channel. (xenbase.org)
Defects1
- Defects in the SCN1B gene, which codes for this beta subunit, are associated with generalized epilepsy with febrile seizures plus, type 1, and Brugada syndrome 5. (nih.gov)
Genes1
- Three genes encode beta subunits (Nabeta1-3), and all three are expressed in the cerebellum. (nih.gov)
Neurons3
- Knockdown of sodium channel Nav1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia. (springer.com)
- Upregulation of the voltage-gated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons. (springer.com)
- The upregulation of voltage-gated sodium channel Na v 1.3 has been linked to hyperexcitability of axotomized dorsal root ganglion (DRG) neurons, which underlies neuropathic pain. (jneurosci.org)
Mediate1
- These channels mediate the first step of active sodium reabsorption essential for the maintenance of body salt and water homeostasis. (qedbio.com)
Blockers1
- Frequently used pain relieving drugs involve sodium channel blockers such as lidocaine, carbamazepine and mexiletine. (biomedcentral.com)
Currents1
- Sodium channels and gating currents. (xenbase.org)
Chloride3
- Reabsorption of sodium chloride is achieved with the sodium chloride/potassium chloride cotransporter, which is driven by the low intracellular concentrations of sodium, chloride, and potassium. (medscape.com)
- Low concentrations are maintained by the basolateral sodium pump (sodium-potassium adenosine triphosphatase), the basolateral chloride channel (ClC-kb), and the apical potassium channel (ROMK). (medscape.com)
- The resting muscle fiber membrane is polarized primarily by the movement of chloride through chloride channels and is repolarized by movement of potassium. (medscape.com)
Auxiliary1
- Na v s are heteromeric proteins composed of a large, pore-forming α-subunits and small β-auxiliary subunits [ 10 , 11 ]. (biomedcentral.com)
Expression3
- Turnock-Jones JJ, Jennings CA, Robbins MJ, Cluderay JE, Cilia J, Reid JL, Taylor A , Jones DN, Emson PC , Southam E. Increased expression of the NR2A NMDA receptor subunit in the prefrontal cortex of rats reared in isolation. (neurotree.org)
- Contactin/F3, a cell adhesion molecule, has been shown to interact with and enhance surface expression of sodium channels Na v 1.2 and Na v 1.9. (jneurosci.org)
- Optogenetic assays provide a flexible, scalable, and information rich approach to probe compound effects for ion channel drug targets in both heterologous expression systems and associated disease relevant cell types. (frontiersin.org)
Reabsorption1
- Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. (qedbio.com)
Inactivation8
- A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation. (xenbase.org)
- These results demonstrate an essential role of Phe-1489 in Na(+)-channel inactivation. (xenbase.org)
- It is proposed that the hydrophobic cluster of Ile-1488, Phe-1489, and Met-1490 serves as a hydrophobic latch that stabilizes the inactivated state in a hinged-lid mechanism of Na(+)-channel inactivation. (xenbase.org)
- Inactivation of the sodium channel. (xenbase.org)
- Destruction of sodium conductance inactivation in squid axons perfused with pronase. (xenbase.org)
- Biophysical and molecular mechanisms of Shaker potassium channel inactivation. (xenbase.org)
- Amino acid residues required for fast Na(+)-channel inactivation: charge neutralizations and deletions in the III-IV linker. (xenbase.org)
- Destruction of the sodium conductance inactivation by a specific protease in perfused nerve fibres from Loligo. (xenbase.org)
Depolarization2
- All forms of familial PP show the final mechanistic pathway involving aberrant depolarization, inactivating sodium channels, and muscle fiber inexcitability. (medscape.com)
- Ion channel dysfunction is usually well compensated with normal excitation, and additional triggers are often necessary to produce muscle inexcitability owing to sustained membrane depolarization. (medscape.com)
Permeable2
- These are selectively and variably permeable ion channels. (medscape.com)
- Biological Function Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride (PubMed:9118951). (qedbio.com)
Isoforms3
- Of the nine distinct channel isoforms described (Na v 1.1 to Na v 1.9), Na v 1.5, Na v 1.8 and Na v 1.9 are resistant to tetrodotoxin (TTX). (biomedcentral.com)
- In order to understand the effects of sodium channels on synaptic signaling and response in the cerebellum, it is essential to know for each class of neuron what sodium channel isoforms are present, and the properties and distribution of each. (nih.gov)
- All sodium channels recorded in the cerebellum are TTX-sensitive with similar kinetics, making it difficult to identify the isoforms electrically. (nih.gov)
Embryonic1
- In this study we show that contactin coimmunoprecipitates with Na v 1.3 from postnatal day 0 rat brain where this channel is abundant, and from human embryonic kidney (HEK) 293 cells stably transfected with Na v 1.3 (HEK-Na v 1.3). (jneurosci.org)
Tetrodotoxin1
- A voltage-dependent gating transition induces use-dependent block by tetrodotoxin of rat IIA sodium channels expressed in Xenopus oocytes. (xenbase.org)
Nav1.61
- Electrophysiological studies suggest that Nav1.6 is responsible for spontaneous firing and bursting features in Purkinje cells, but the specialized functions of the other subunits in the cerebellum remain unknown. (nih.gov)