Antiporter
As with sodium in this example, antiporters rely on an established gradient that makes entry of one ion energetically favorable to force the unfavorable movement of a second molecule in the opposite direction.
[2] Though ATP-powered pumps also move molecules in an energetically unfavorable direction and undergo conformational changes to do so, they fall under a different category of membrane proteins because they couple the energy derived from ATP hydrolysis to transport their respective ions.
One of these is multiple transmembrane regions that span the lipid bilayer of the plasma membrane and form a channel through which hydrophilic molecules can pass.
The early studies took place in the mid-20th century and were focused on the mechanisms that transported ions such as sodium, potassium, and calcium across the plasma membrane.
Researchers made the observation that these ions were moved in opposite directions and hypothesized the existence of membrane proteins that could facilitate this type of transport.
Through purification from bovine heart mitochondria, Racker and his colleagues found a mitochondrial protein that could exchange inorganic phosphate for hydroxide ions.
[4][19] For example, when NCX functions during excitotoxicity, this characteristic allows it to have a protective effect because the accompanying increase in intracellular calcium levels enables the exchanger to work in its normal direction regardless of the sodium concentration.
[4] Another example is the depolarization of cardiac muscle cells, which is accompanied by a large increase in the intracellular sodium concentration that causes NCX to work in reverse.
[21] Arrhythmias can occur when calcium is not properly exported by NCX, causing delayed afterdepolarizations and triggering abnormal activity that can possibly lead to atrial fibrillation and ventricular tachycardia.
Its dysfunction can result in oxidative stress and neuronal cell death, contributing to the cognitive decline that characterizes Alzheimer's disease.
[25] The abnormal calcium handling of atypical NCX function can also cause the mitochondrial dysfunction, oxidative stress, and neuronal cell death that characterize Parkinson's.
The sodium-hydrogen antiporter's function is upregulated by Angiotensin II in the proximal convoluted tubule when the body needs to reabsorb sodium and excrete hydrogen.
[31] For the organisms to maintain homeostasis and carry out crucial functions, Na+/H+ antiporters are used to rid the cytoplasm of excess sodium by pumping Na+ out of the cell.
[31] Dysregulation of the sodium-hydrogen antiporter's activity has been linked to cardiovascular diseases, renal disorders, and neurological conditions [29] NHE inhibitors are being developed to treat these issues.
[34] RTA is characterized by the inability of the kidneys to acidify the urine due to underactive NHE3 and reduced secretion of hydrogen ions, resulting in metabolic acidosis.
The level of tau phosphorylation was also found to be elevated, which leads to the formation of insoluble tangles that can cause neuronal damage and death.
The chloride-bicarbonate antiporter is crucial to maintaining pH and fluid balance through its function of exchanging bicarbonate and chloride ions through cell membranes.
It is found in the intestinal mucosa, especially in the columnar epithelium and goblet cells of the apical surface of the membrane, where it carries out the function of chloride and bicarbonate exchange.
This exchanger is found in red blood cells, where it helps transport bicarbonate and carbon dioxide between the lungs and tissues to maintain acid-base homeostasis.
[41] Because of its importance to the reabsorption of water in the intestine, mutations in protein DRA cause a condition called congenital chloride diarrhea (CCD).
Mutations of kidney AE1 can lead to distal renal tubular acidosis, a disorder characterized by the inability to secrete acid into the urine.
[44] Finally, overhydrated hereditary stomatocytosis is a rare genetic disorder where red blood cells have an abnormally high volume, leading to changes in hydration status.
Its roles are not entirely clear, but CLC-4 has been found to possibly participate in endosomal acidification, transferrin trafficking, renal endocytosis, and the hepatic secretory pathway.
It shares 80% of its amino acid sequence with CLC-3 and CLC-4, but it is mainly found in the kidney, especially in the proximal tubule, collecting duct, and ascending limb of the loop of Henle.
[48][49] Dent's disease itself is one of the causes of Fanconi syndrome, which occurs when the proximal convoluted tubules of the kidney do not perform an adequate level of reabsorption.
These mice were smaller, had shortened long bones, disorganized trabecular structure, a missing medullary cavity, and their teeth did not erupt.
[52] The RFC protein is critical because folates take the form of hydrophilic anions at physiological pH, so they do not diffuse naturally across biological membranes.
[53] Because folates are essential for various life-sustaining processes, a deficiency in this molecule can lead to fetal abnormalities, neurological disorders, cardiovascular disease, and cancer.
This family of proteins includes three isoforms, VGLUT1, VGLUT2, and VGLUT3, that are responsible for packaging glutamate - the most abundant excitatory neurotransmitter in the brain - into synaptic vesicles.
The nucleus accumbens, pars compacta of the substantia nigra, and ventral tegmental area - all subregions of the brain involved in clinical depression - were found to have lower VMAT2 levels.
