Ion Transport Capability Research Articles

Epidermal Growth Factor Partially Restores Colonic Ion Transport Responses in Mouse Models of Chronic Colitis

Epidermal growth factor receptor (EGFR) activation, which plays an important role in regulating intestinal ion transport, can alleviate clinical symptoms such as diarrhea in patients with ulcerative colitis and promote mucosal restitution in animal models of colitis. Here, we investigate whether EGFR can regulate colonic ion transport in the setting of colitis. Distal colon from control mice and mice with colitis was retained for immunohistochemistry or mounted in Ussing chambers. Ion transport responses across the tissues to the calcium agonist carbachol and the adenosine 3',5'-cyclic monophosphate agonist forskolin were measured with or without epidermal growth factor (EGF) pretreatment. EGF pretreatment of normal colonic mucosa inhibited ion transport responses to carbachol and forskolin but potentiated the reduced ion transport responses seen in dextran sulfate sodium (DSS)-treated and mdr1a knockout mouse colon. Ion substitution studies and the sodium transport inhibitor amiloride showed that sodium movement primarily accounted for the potentiating effect of EGF in DSS-treated tissues, despite decreased sodium channel expression. EGF potentiation of transport responses in DSS-treated colon was completely blocked by the cytoskeletal disruptor cytochalasin D and the phosphatidylinositol 3-kinase inhibitor wortmannin, whereas the novel and conventional protein kinase C isoform inhibitor Gö6850 and the extracellular signal-regulated kinase inhibitor PD98059 partially reduced EGF effects. EGFR epithelial distribution and transforming growth factor alpha expression were also altered in DSS-treated tissues. Chronic inflammation uncovers a potentiating effect of EGFR activation on epithelial electrogenic sodium absorption that would be expected to ameliorate diarrheal symptoms associated with colitis.

Ageing choroid plexus-cerebrospinal fluid system.

The impact of ageing on the choroid plexus (CP)-CSF circulatory system has largely been un-investigated, or has been of interest only in relation to neurological disease. This paper reviews the evidence for age-related changes to the CP-CSF system and compares changes with disease states where appropriate. The changes discussed include reduced ion transport capabilities, evidence for oxidative stress, altered hormone interactions, decreased CSF secretion rates in animal models and the contradictory nature of human data, reduced clearance of protein from CSF, and slower fluid turnover. The potential impacts of these changes are highlighted, including the possibility of reduced resistance to stress insults and slow clearance of toxic compounds from CSF with specific reference to amyloid peptide. Other impacts may include the reduced ability of CSF to act as a circulating medium for hormone and growth factors to reach their brain targets, and reduced homeostasis of CSF nutrients (amino acids, vitamins), which might influence brain interstitial fluid homeostasis.

Modulation of epithelial permeability by extracellular macromolecules.

Epithelia are sheets of cells joined together by tight junctions. This geometry allows an epithelium to act as a barrier, i.e., restrict the movement of substances between two compartments that it separates (typically 1 compartment is the blood) and also to actively and selectively transport substances between the two compartments. It has been known for a number of years that both the barrier and transport functions of epithelia can be regulated by hormones and neurotransmitters, and this regulation is a central component of plasma electrolyte and nonelectrolyte homeostasis. Less appreciated is that these epithelial functions can be modified by macromolecules other than neurotransmitters and hormones. These macromolecules have been divided into the following categories: proteases, cytokines, cellular constituents, nonbacterial xenobiotics, and bacterial xenobiotics. Such macromolecules can alter epithelial transport and barrier function by a number of different mechanisms. These include proteolysis of epithelial ion channels and tight junctional complexes, conversion of an ion pump into a nonselective cation channel, increase in epithelial membrane permeability resulting in cell swelling and lysis, and up- or downregulation of cellular second messenger systems that can alter ion transport capabilities or prove cytotoxic to the cells. Finally, these modifications can be either transient or chronic in nature and in many circumstances result in a perturbation of the electrolyte and nonelectrolyte status of the host organism.

Branchial chloride cell proliferation in the rainbow trout, Oncorhynchus mykiss: implications for gas transfer

The effects of branchial chloride cell proliferation on ion transport capability and gill morphometry were evaluated in the rainbow trout, Oncorhynchus mykiss, to test the hypothesis that chloride cell (CC) proliferation benefits ionic regulation at the expense of efficient gas transfer. The extent of hormone-induced CC proliferation (using ovine growth hormone (oGH), cortisol, or a combination of both) on the gill filament epithelium was assessed by determining the fractional surface area of exposed cells using scanning electron microscopy. Cortisol and oGH were equally effective in increasing CC fractional surface area (~2×), owing to the enlargement of individual CCs. The combined cortisol/oGH treatment resulted in an even greater increase in CC fractional area (~6×), as both the size and number of CCs increased. Sham injections were without effect on CC surface area or number. Significant increases in Na+ (Jin Na+) and Cl− uptake (Jin Cl−) were observed after all hormone treatments and were correlated positively with the increases in the CC fractional surface area. These findings support the view that CC proliferation enhances branchial ion transport capability. Lamellar epithelial thickness (measured by transmission electron microscopy) was increased in hormone-treated fish, while lamellar surface area (measured using light microscopy) was unaffected. The area of the interlamellar water channels (calculated from light micrographs) was significantly reduced in hormone-treated fish. These results suggest that, in trout, a compromise is made between the efficiency of ion regulation and gas transfer in which the enlargement/proliferation of CCs may impede gas transfer.

Gene transfection of lung cells in vitro and in vivo.

This review focuses on the use of gene transfection as a tool with which to examine pulmonary function at the molecular, cellular, and whole organ level. The term transfection is defined as the introduction of one or more copies of a gene or cDNA into eukaryotic cells in order to permit either transient or permanent transcription and, usually, translation of a gene product, whose presence can be detected directly or inferred from functional assays. Although the term has also been applied to the introduction of DNA into embryonal cells to produce trans genic animals, this topic is not discussed in our review. Rather we describe various transfection techniques as well as experiments in which transfection-based methods have yielded new insights into pulmonary biology. We also discuss recent reports of successful in vivo lung cell transfection. In general, there are three reasons to consider gene transfection as an experimental approach. First, DNA can be transfected into a eukaryotic cell in order to produce a normal or mutated protein; the protein can then be characterized in terms of its structure and function in a physiologically relevant context. Two experiments utilizing the cystic fibrosis (CF) transmembrane conductance regulator (CFfR) gene illustrate this approach. In the first experiment, the CFfR cDNA was transfected into cells that lacked cAMP­ regulated chloride conductance (1 , 2); this ion transport capability is known to be absent or reduced in cells obtained from patients with CF. Both

Solid state electroactive materials: synthesis and solid state electroactivity of some new materials derived from tris(2,2′-bipyridine- N, N′-dioxide)iron(III)-(IV) and hexacyanoferrate(II)-(III)

The synthesis of new solid electroactive materials of mixed-valent multinuclear inorganic backbones, derived from tris(2,2′-bipyridine- N, N′-dioxide)iron(III) tris(2,2′-bipyridine- N, N′-dioxide)iron(IV), hexacyanoferrate(II) and hexacyanoferrate(III) in the presence of perchlorate and/or chloride salts of sodium and/or potassium, are reported. The solid state cyclic voltammetry results show that thin powder layers of some of these solid materials possess good conducting properties ( i.e. varying degrees of electron conduction and/or ion conduction) at room temperature as a result of simultaneous electron and ion transport capabilities generated during redox.

Effect of acid stress on sodium transport by isolated skins and on osmotic permeability of intact frogs.

The experiments reported here were designed to determine the effects of increased external hydrogen ion concentrations on the ion transport capability of isolated frog skins measured as short-circuit current and to determine the nature of the interaction of hydrogen ions to sodium transport. Results from a study of the effects of acid exposure on the osmotic permeability of intact frogs are also reported.