Nutrition Guide

Sodium channel, voltage gated, type X, alpha subunit (SCN10A) is a human gene encoding the Nav1.8 protein. Nav1.8, is a sodium channel subunit.

Ryanodine receptor 2 (cardiac), also known as RYR2, is a human gene.

This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with catecholaminergic polymorphic ventricular tachycardia, stress-induced polymorphic ventricular tachycardia, and arrhythmogenic right ventricular dysplasia.[1]

Ryanodine receptor 3, also known as RYR3, is a human gene.[1] The protein encoded by this gene is both a calcium channel and a receptor for the plant alkaloid ryanodine. RYR3 along with RYR1 control the resting calcium ion concentration in skeletal muscle.[2]

Ryanodine receptor 1 (skeletal), also known as RYR1, is a human gene.

This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described.[1]

ROMK is an acronym for the Renal Outer Medullary Potassium channel. This is an ATP-dependent potassium channel (Kir1.1) that transports potassium out of cells.

It plays an important role in potassium recycling in the thick ascending limb (TAL) and potassium secretion in the cortical collecting duct (CCD) of the nephron.

Proton channels are ion channels for protons. Most prominent are the voltage-gated proton channels.

Polycystic kidney disease 1 (autosomal dominant), also known as PKD1, is a human

This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It may function as an integral membrane protein involved in cell-cell/matrix interactions, and may modulate intracellular calcium homoeostasis and other signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene have been associated with autosomal dominant polycystic kidney disease. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described.[1]

The sensitivity of P2X receptors to ATP is strongly modulated by changes in extracellular pH and by the presence of heavy metals (e.g. zinc and cadmium). For example, the ATP sensitivity of P2X1, P2X3 and P2X4 receptors is attenuated when the extracellular pH<7, whereas the ATP sensitivity of P2X2 is significantly increased. On the other hand, zinc potentiates ATP-gated currents through P2X2, P2X3 and P2X4, and inhibits currents through P2X1. The allosteric modulation of P2X receptors by pH and metals appears to be conferred by the presence of histidine side chains in the extracellular domain.[1] In contrast to the other members of the P2X receptor family, P2X4 receptors are also very sensitive to modulation by the macrocyclic lactone, ivermectin.[11] Ivermectin potentiates ATP-gated currents through P2X4 receptors by increasing the open probability of the channel in the presence of ATP, which it appears to do by interacting with the transmembrane domains from within the lipid bilayer.[12]

ATP binds to the extracellular loop of the P2X receptor, whereupon it evokes a conformational change in the structure of the ion channel that results in the opening of the ion-permeable pore. This allows cations such as Na+ and Ca2+ to enter the cell, leading to depolarization of the cell membrane and the activation of various Ca2+-sensitive intracellular processes. The channel opening time is dependent upon the subunit makeup of the receptor. For example, P2X1 and P2X3 receptors desensitize rapidly (a few hundred milliseconds) in the continued presence of ATP, whereas the P2X2 receptor channel remains open for as long as ATP is bound to it. Three ATP molecules are thought to be required to activate a P2X receptor, suggesting that ATP needs to bind to each of the three subunits in order to open the channel pore, though recent evidence suggests that ATP binds at the three subunit interfaces.[10] The precise mechanism by which the binding of ATP leads to the opening of the P2X receptor channel pore is not well understood, but is currently under investigation.

In keeping with their wide distribution throughout the body, P2X receptors are involved in a variety of physiological processes,[1][7] including:
Modulation of cardiac rhythm and contractility[8]
Modulation of vascular tone[1]
Mediation of nociception[9] - e.g. hypersensitivity to innocuous stimuli following upregulation of P2X4 in the spinal cord
Contraction of the vas deferens during ejaculation[1]