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  • This review aims to examine

    2019-07-11

    This review aims to examine the literature on chloride ISRIB in the context of transplacental transport. After a short overview of the general cellular functions of Cl− channels in epithelia and the molecular classifications of these channels, it will focus on the evidence for the presence of chloride channels in placental tissue and the specific characteristics of these channels, including pharmacology and possible roles in the placental physiology. This review will also discuss placental chloride channels from pathological placentae and provides a short account of the family of intracellular Cl− channels reported in trophoblast. Finally, it will summarize the main transport mechanisms for Cl− exchange by conductive pathways in hSTB membranes proposed to date.
    Background of chloride channels Anion selective channels have been classified into several group based on functional properties such as voltage dependence, single conductance, selectivity, sensitivity to blockers, kinetics, molecular structures and subcellular localization. Electrophysiological and families of gene studies of anion channels have revealed a wide variety of differences in their biophysical properties, for example single-channel conductance, regulation mechanisms or pharmacological sensitivity. These channels are integral proteins in biological membranes and, like other channels, the anion channels may be present and execute their functions in the plasma membrane or in intracellular organelle membranes. Ion transport through channels occurs via diffusional ion flux down the electrochemical gradient of the ion, meaning that a combination of the membrane potential and the difference between cytoplasmic and extracellular Cl− concentrations, determines whether the opening of a Cl− channel will lead to an influx or efflux of this ion. Chloride channels may conduct other anions better than they conduct chloride, but are so named because chloride is the most abundant anion in tissues. The functions of chloride channels, as well as those of other transporter proteins such as pumps, carriers and other channels, include cell volume regulation, ionic homeostasis, transepithelial transport, regulation of electrical excitability, secretion, absorption, etc. Their function and biophysical properties have determined their classification. For instance, the “apical chloride channel in absorptive epithelia” was described as a channel with a large single-channel conductance and that was active on a membrane potential ISRIB near 0mV. This channel, also present in placenta is the Maxi-chloride channel, so named for its very high conductance. The classification of chloride channels has changed as more information has become available. Currently, several gene families of chloride channels are known. For example, the CLC family in mammals has, at least, nine members present in the plasma membrane or in intracellular organelles [5], [6]. In their review “Molecular structure and physiological function of chloride channels” [7], Jentsch et al. classified channels in the CLC chloride channel family, the cystic fibrosis chloride channel, swelling active chloride channels, calcium activated chloride channels and ligand gated chloride channels. As mentioned before, transport of anions across cellular membranes is crucial for various functions. Alterations in their structure due to mutations in Cl− channels or in their environment can cause diseases such as the muscle disorder myotonia, cystic fibrosis, renal salt loss in Bartter syndrome, kidney stones, deafness and the bone disease osteopetrosis [8].
    Placenta and transport The placenta is an organ formed on the wall of the uterus during pregnancy; at term, it is approximately 20cm in diameter and 500–700g in mass and has a complex structure. It is the fetal–maternal interface for all mammals, including humans. It has multiples functions, among them it is responsible for the solute exchange between the mother and the fetus.