Ion Channels In Epithelial Cells Research Articles

Ion Channels in Epithelial Dynamics and Morphogenesis.

Mechanosensitive ion channels mediate the neuronal sensation of mechanical signals such as sound, touch, and pain. Recent studies point to a function of these channel proteins in cell types and tissues in addition to the nervous system, such as epithelia, where they have been little studied, and their role has remained elusive. Dynamic epithelia are intrinsically exposed to mechanical forces. A response to pull and push is assumed to constitute an essential part of morphogenetic movements of epithelial tissues, for example. Mechano-gated channels may participate in sensing and responding to such forces. In this review, focusing on Drosophila, we highlight recent results that will guide further investigations concerned with the mechanistic role of these ion channels in epithelial cells.

Paracellular epithelial sodium transport maximizes energy efficiency in the kidney.

Efficient oxygen utilization in the kidney may be supported by paracellular epithelial transport, a form of passive diffusion that is driven by preexisting transepithelial electrochemical gradients. Claudins are tight-junction transmembrane proteins that act as paracellular ion channels in epithelial cells. In the proximal tubule (PT) of the kidney, claudin-2 mediates paracellular sodium reabsorption. Here, we used murine models to investigate the role of claudin-2 in maintaining energy efficiency in the kidney. We found that claudin-2-null mice conserve sodium to the same extent as WT mice, even during profound dietary sodium depletion, as a result of the upregulation of transcellular Na-K-2Cl transport activity in the thick ascending limb of Henle. We hypothesized that shifting sodium transport to transcellular pathways would lead to increased whole-kidney oxygen consumption. Indeed, compared with control animals, oxygen consumption in the kidneys of claudin-2-null mice was markedly increased, resulting in medullary hypoxia. Furthermore, tubular injury in kidneys subjected to bilateral renal ischemia-reperfusion injury was more severe in the absence of claudin-2. Our results indicate that paracellular transport in the PT is required for efficient utilization of oxygen in the service of sodium transport. We speculate that paracellular permeability may have evolved as a general strategy in epithelial tissues to maximize energy efficiency.

Ion channels in epithelial cells of the choroid plexus isolated from the lateral ventricle of rat brain

Whole-cell patch clamp methods were used to determine the expression of ion channels in the epithelial cells of choroid plexus isolated from the lateral ventricle of the rat brain. A single population of cells with a mean capacitance of 61.5±1.7 pF was identified in 103 recordings. This value is significantly greater than that measured for cells from the fourth ventricle ( P<0.0l by unpaired t-test), indicating that cells from the lateral ventricle have a greater surface area. Voltage-dependent, outward currents were recorded using a K +-rich electrode solution. These currents were partially inhibited by 10 nM margatoxin or 10 nM dendrotoxin-K and blocked by 5 mM TEA +. An inward-rectifying chloride conductance was observed in K +-free solutions. The relative permeability of this conductance to anions was P I> P Cl> P aspartate. A volume-sensitive anion conductance was observed when cell swelling was induced using a hypertonic electrode solution. The properties of each conductance were similar to conductances previously identified in fourth ventricle choroid plexus cells. Furthermore, there were no significant differences between the magnitudes of any of the conductances in cells from the lateral and fourth ventricle choroid plexus. Thus, the ionic conductances expressed in rat lateral and fourth ventricle choroid plexus are very similar.

A PDZ-interacting domain in CFTR is an apical membrane polarization signal.

Polarization of the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel, to the apical plasma membrane of epithelial cells is critical for vectorial transport of chloride in a variety of epithelia, including the airway, pancreas, intestine, and kidney. However, the motifs that localize CFTR to the apical membrane are unknown. We report that the last 3 amino acids in the COOH-terminus of CFTR (T-R-L) comprise a PDZ-interacting domain that is required for the polarization of CFTR to the apical plasma membrane in human airway and kidney epithelial cells. In addition, the CFTR mutant, S1455X, which lacks the 26 COOH-terminal amino acids, including the PDZ-interacting domain, is mispolarized to the lateral membrane. We also demonstrate that CFTR binds to ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50), an apical membrane PDZ domain-containing protein. We propose that COOH-terminal deletions of CFTR, which represent about 10% of CFTR mutations, result in defective vectorial chloride transport, partly by altering the polarized distribution of CFTR in epithelial cells. Moreover, our data demonstrate that PDZ-interacting domains and PDZ domain-containing proteins play a key role in the apical polarization of ion channels in epithelial cells.

The Isolation and Characterization of a Novel Corticostatin/Defensin-like Peptide from the Kidney

We report the isolation and characterization of RK-1, a novel peptide found in the kidney. RK-1 is related to the corticostatin/defensins and has the sequence MPC-SCKKYCDPWEVIDGSCGLFNSKYCCREK but differs from the very cationic corticostatins/defensins in having only one arginine and a calculated charge at pH 7 of +1. Like some myeloid corticostatin/defensins RK-1 inhibits the growth of Escherichia coli. Since corticostatin/defensins effect ion flux in responsive epithelia we used volume changes in villus enterocytes as a model system to study the effects of RK-1 on ion channels in epithelial cells. At concentrations > or = 10(-9) M RK-1 decreased enterocyte volume in a dose-dependent manner through a pathway that requires extracellular calcium and is inhibited by niguldipine, a dihydropyridine-sensitive "L"-type Ca(2+)-channel blocker. In other assay systems for corticostatin-defensins, such as the inhibition of adrenocorticotropin-stimulated steroidogenesis, or cell lysis, RK-1 was inactive or only weakly active. These results demonstrate the existence of a novel system of biologically active peptides in the kidney represented by RK-1 which is antimicrobial and can activate epithelial ion channels in vitro.

Regulation of chloride secretion in mammalian colon

A number of procedures or interventions which activate electrogenic ion transport in mammalian intestine are reviewed. Using in vitro models it is possible to demonstrate direct or indirect pathways to stimulate chloride secretion. Such activation, in vivo, would change the gut from a state of net water absorption to one of fluid secretion. The movement of water is driven by electrical and osmotic gradients set up as a consequence of opening regulated ion channels in epithelial cells. Secretagogues may govern epithelial intracellular second messenger pathways to regulate ion channel activity directly or by activation of membrane bound receptors on the surface of epithelial cells. In health or disease secretagogues may be derived from cells within the attendant lamina propria of the intestinal mucosa. Pharmacological techniques may be employed to determine which mediators contribute to indirect stimulation of electrogenic ion transport by activation of neurons or of immunocytes (mast cells or phagocytes). Dissection and reconstruction of models of intestinal hypersensitivity reactions show that neuro-immune networks which regulate intestinal ion transport appear to be complex, functionally integrated systems. Analysis of such interactions may identify cellular or humoral targets with which to examine novel diagnostic, preventative or therapeutic strategies with regard to intestinal diseases.

Ion Channels and Colonic Salt Transport

The focus of this review is the ion transport functions of the vertebrate colon, in particular the role of ion channels in the maintenance and regulation of ion transport processes. A great deal has been learned in the last decade about the properties of ion channels in epithelial cells, and it seems appropriate to review our current understanding of the function of these elements in colonic epithelial transport. I like to think of epithelial ion channels in general, and colonic ion channels in particular, as working class ion channels. While neuronal ion channels are up in the penthouse subserving a variety of cerebral functions, the channels that inhabit colonic epithelial cells are quietly at work doing the tedious, but nevertheless necessary, jobs associated with preserving electrolyte balance . Absorption and Secretion

Absence of acetylcholine‐induced current in epithelial cells from thymus glands and thymomas of myasthenia gravis patients

We investigated the activity of ion channels in epithelial cells from human thymus glands and thymomas kept in short-term cell culture by clamping the membrane potential of the cells at -85 mV and determining the membrane current flowing on application of acetylcholine, glycine, or gamma-aminobutyric acid. In concentrations of up to 10(-3) M, none of the neurotransmitters induced any detectable current. This suggests (1) that there are no acetylcholine receptors (AChRs) or other products of the AChR gene family having ion-channel properties in the membranes of these epithelial cells, and (2) that the alpha-bungarotoxin-binding protein of thymus and thymoma has no AChR-like ion-channel property. These results support the hypothesis that the cross-reacting structures that elicit the anti-AChR autoimmune response in thymoma-associated myasthenia gravis are antigens having only limited homology with the AChR. Myasthenia gravis not associated with thymoma might have a different pathogenesis.

Volume-Regulatory Ion Channels in Epithelial Cells

Patch-clamp studies showed that the regulatory volume decrease process is closely associated with functions of K+, Cl-, and Ca2+-permeable channels in epithelial cells. Na+-permeable channels in the regulatory volume increase process may also be involved, as deduced from whole cell recordings using intestinal epithelial cells.

Ion channels in epithelial cells from thymus and thymomas of myasthenia gravis patients

Ion channels in epithelial cells from thymus and thymomas of myasthenia gravis patients