title: Copper ion redox state is critical for its effects on ion transport pathways and methaemoglobin formation in trout erythrocytes.
abstract: We have studied the mechanism of copper uptake by the cells, its oxidative action and effects on ion transport systems using rainbow trout erythrocytes. Cupric ions enter trout erythrocytes as negatively charged complexes with chloride and hydroxyl anions via the band 3-mediated Cl-/HCO3- exchanger. Replacement of Cl- by gluconate, and complexation of cupric ions with histidine abolish rapid Cu2+ uptake. Within the cell cupric ions interact with haemoglobin, causing methaemoglobin formation by direct electron transfer from heme Fe2+ to Cu2+, and consecutive proton release. Ascorbate-mediated reduction of cupric ions to cuprous decreases copper-induced metHb formation and proton release. Moreover, cuprous ions stimulate Na+H+ exchange and residual Na+ transport causing net Na+ accumulation in the cells. The effect requires copper binding to an externally facing thiol group. Copper-induced Na+ accumulation is accompanied by K+ loss occurring mainly via K+-Cl- cotransporter. Taurine efflux is also stimulated by copper exposure. However, net loss of osmolytes is not as pronounced as Na+ uptake and modest swelling of the cells occurs after 5 min of copper exposure. Taken together the results indicate that copper toxicity, including copper transport into the cells and its interactions with ion transport processes, depend on the valency and complex formation of copper ions.
authors.affiliation: Laboratory of Animal Physiology, Department of Mathematics and Natural Sciences, University of Turku, FIN-20014 Turku, Finland. annab@physiol.unizh.ch
authors.forename: Anna Yu
authors.initials: AY
authors.lastname: Bogdanova
authors.forename: Max
authors.initials: M
authors.lastname: Gassmann
authors.forename: Mikko
authors.initials: M
authors.lastname: Nikinmaa
mesh_terms: D000818:Animals; D048429:Cell Size; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005110:Extracellular Space; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D008706:Methemoglobin / Q000096:biosynthesis*; D017686:Oncorhynchus mykiss; D010084:Oxidation-Reduction; D011188:Potassium / Q000097:blood
chemical_list: D003300:Copper; D008706:Methemoglobin; D011188:Potassium