Abstract
There is a long history of interest in the interaction of toxic metals with membranes for two reasons. First, it was recognized early on that plasma membranes of cells were important potential targets for metals and that the effects of metals on membrane proteins might provide a basis for understanding the diverse toxic effects of these substances on the nervous system, the kidney, and the GI tract (CLarkson 1972; FOulkes 1986; KInter and PRitchard 1977; OEhme 1978; ROthstein 1970; TEmpleton and CHerian 1983). Equally important historically, however, has been the interest of membrane physiologists in metals, particularly mercurials, as probes of membrane proteins that could be used experimentally to investigate mechanisms of transport and cellular homeostasis (CUrran 1972; FErreira 1978; FRenkel et al. 1975; HIllyard et al. 1979; ROthstein 1970; SChaeffer et al. 1973; SCholtz and ZEiske 1988; SChwartz and FLamenbaum 1976; STirling 1975). A major problem in both areas, however, has been the multiplicity of actions of metals on cell membranes; so that specific sites of action and cause-and-effect relationships have been difficult to sort out. As a result there appears to be a relatively large literature implicating biological membranes as sites of action for metals, but the mechanistic details of the cellular effects that lead to modulation of transport and ultimately to organ dysfunction have not been clearly defined.
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References
Aiken SP, Horn NM Saunders NR (1992) Effects of amino acids on zinc transport in rat erythrocytes. J Physiol (Lond) 445:69–80
Akabas MH, Stauffer DA, Xu M, Karlin A (1992) Acetylcholine receptor channel structure probed in cysteine-substitution mutants. Science 258:307–310
Alda Torrubia JO, Garay R (1989) Evidence for a major route for zinc uptake in human red blood cells:[Zn(HCO3)2 Cl]− influx through the [Cl−/HCO3 −] anion exchanger. J Cell Physiol 138:316–322
Alda Torrubia JO, Garay R (1990) Chloride (or bicarbonate)-dependent copper uptake through the anion exchanger in human red blood cells. Am J Physiol 259:C570–C576
Anner BM, Moosmayer M (1992) Mercury inhibits Na-K-ATPase primarily at the cytoplasmic side. Am J Physiol 262:F843–F848
Anner BM, Moosmayer M, Imesch E (1992) Mercury blocks Na-K-ATPase by a ligand-dependent and reversible mechanism. Am J Physiol 262. F830–F836
Ballatori N (1991) Mechanisms of metal transport across liver cell plasma membranes. Drug Metabol Rev 23(1,2):83–132
Ballatori N (1994) Glutathione mercaptides as transport forms of metals. In:Anders MW, Dekant W (eds) Conjugation-dependent carcinogenicity and toxicity of foreign compounds. Academic, Florida, pp 271–298
Ballatori N, Clarkson TW (1983) Biliary transport of glutathione and methyl-mercury. Am J Physiol 244:G435–G441
Ballatori N, Shi C, Boyer JL (1988) Altered plasma membrane ion permeability in mercury-induced cell injury:studies in hepatocytes of elasmobranch Raja erinacea. Toxicol Appl Pharmacol 95:279–291
Benndorf K, Nilius B (1988) Different blocking effects of Cd++ and Hg++ on the early outward current in myocardial mouse cells. Gen Physiol Biophys 7:345–352
Blazka ME, Shaikh ZA (1991) Differences in cadmium and mercury uptakes by hepatocytes:role of calcium channels. Toxicol Appl Pharmacol 110:355–363
Brunder DG, Dettbarn C, Palade P (1988) heavy metal-induced Ca2+ release from sarcoplasmic reticulum. J Biol Chem 263:18785–18792
Butler JN (1964) Introduction to complex formation equilibria. Ionic equilibrium, a mathematical approach. Addison-Wesley, Reading, Massachusetts Palo Alto London, p 261
Chang D, Dawson DC (1988) Digitonin-permeabilized colonic cell layers. J Gen Physiol 92:281–306
Chang D, Betz L, Dawson DC (1985) Mercury reversibly blocks apical K channels in the urinary bladder of the winter flounder, Pseudopleuronectes americanus. Bull Mt Des Isl Biol Lab 25:44–45
Chiles TC, Dudeck-Collart KL, Kilberg MS (1988) Inactivation of amino acid transport in rat hepatocytes and hepatoma cells by PCMBS. Am J Physiol 255:C340–C345
Clarkson TW (1972) The pharmacology of mercury compounds. Annu Rev Pharmacol 22:375–406
Clarkson TW (1993) Molecular and ionic mimicry of toxic metals. Annu Rev Pharmacol Toxicol 32:545–571
Crofts JN, Barritt GJ (1990) The liver cell plasma membrane Ca2+ inflow systems exhibit a broad specificity for divalent metal ions. Biochem J 269:579–587
Curran PF (1972) Effect of silver ion on permeability properties of frog skin. Biochim Biophys Acta 288:97
Darwish HM, Cheney JC, Schmitt RC, Ettinger MJ (1984) Mobilization of copper (II) from plasma components and mechanism of hepatic copper transport. Am J Physiol 246:G72–G79
Delmondedieu M, Boudou A, Desmazes J-P, Georgescauld D (1989) Interaction of mercury chloride with the primary amine group of model membranes containing phosphatidylserine and phosphatidylethanolamine. Biochim Biophys Acta 986:191–199
Dutczak WJ, Ballatori N (1994) Transport of the glutathione-methylmercury complex across liver canalicular membranes on GSH carriers. J Biol Chem 269:9746–9751
Ferreira KTG (1978) The effect of copper on frog skin. The role of sulfhydryl groups. Biochim Biophys Acta 510:298–304
Flanagan JL, Friedman PA (1991) Pathathyroid hormone-stimulated cadmium accumulation in Madin-Darby canine kidney cells. Toxicol Appl Pharmacol 109:241–250
Foulkes EC (1986) Cadmium. In:Born GVR, Farah A, Herken H, Welch AD (eds) Handbook of experimental pharmacology. Springer, Berlin Heidelberg New York, p 400
Frame MDS, Milanick MA (1991) Mn and Cd transport by the Na-Ca exchanger of ferret red blood cells. Am J Physiol 261:C467–C475
Frenkel A, Ekblad EBM, Edelman IS (1975) Effects of sulfhydryl reagents on basal and vasopressin-stimulated Na+ transport in the toad bladder. In:Eisenberg H, Katchalski-Katair E, Manson LA (eds) Biomembranes, vol 7. Plenum, New York, pp 61–80
Fukuda J, Kawa K (1977) Permeation of manganese, cadmium, zinc, and beryllium through calcium channels of an insect muscle membrane. Science 196:309–311
Gamba G, Saltzberg SN, Lombardi M, Miyanoshita A, Lytton J, Hediger MA, Brenner BM, Hebert SC (1993) Primary structure and functional expression of a cDNA encoding the thiazide-sensitive, electroneutral sodium-chloride cotransporter. Proc Natl Acad Sci USA 90:2749–2753
Gregus Z, Stein AF, Varga F, Klaassen CD (1992) Effect of lipoic acid on biliary excretion of glutathione and metals. Toxicol Appl Pharmacol 114:88–96
Gutknecht J (1981) Inorganic mercury (Hg2+) transport through lipid bilayer membranes. J Membr Biol 61:61–66
Hillyard SD, Sera R, Gonick HC (1979) Effects of Cd++ on short-circuit current across epithelial membranes. II. Studies with the isolated frog skin epithelium, urinary bladder, and large intestine. J Membr Biol 46:283–294
Hinkle PM, Kinsella PA, Osterhoudt KC (1987) Cadmium uptake and toxicity via voltage-sensitive calcium channels. J Biol Chem 262:16333–16337
Hinkle PM, Shanshala ED II, Nelson EJ (1992) Measurement of intracellular cadmium with fluorescent dyes. J Biol Chem 267:25553–25559
Hughes BP, Barritt GJ (1989) Inhibition of the liver cell receptor-activated Ca2+ inflow system by metal ion inhibitors of voltage-operated Ca2+ channels but not by other inhibitors of Ca2+ inflow. Biochim Biophys Acta 1013:197–205
Hughes WH (1957) A physiochemical rationale for the biological activity of mercury and its compounds. Ann NY Acad Sci 65:454–460
Hurwitz L (1986) Pharmacology of calcium channels and smooth muscle. Annu Rev Pharmacol Toxicol 26:225–258
Imesch E, Moosmayer M, Anner BM (1992) Mercury weakens membrane anchoring of Na-K-ATPase. Am J Physiol 262. F837–F842
Jungwirth A, Ritter M, Lang F (1991a) Influence of mercury ions on electrical properties of rat proximal and distal renal tubules. Nephron 58:229–232
Jungwirth A, Ritter M, Paulmichl M, Lang F (1991b) Activation of cell membrane potassium conductance by mercury in cultured renal epitheloid ( MDCK) cells. J Cell Physiol 146:25–33
Kalfakakou V, Simons TJB (1990) Anionic mechanisms of zinc uptake across the human red cell membrane. J Physiol (Lond) 421:485–497
Karniski LP (1992) Hg2+ and Cu+ are ionophores, mediating CP−/OH− exchange in liposomes and rabbit renal brush border membranes. J Biol Chem 267:19218–19225
Kaur P, Rosen BP (1992) Plasmid-encoded resistance to arsenic and antimony. Plasmid 27:29–40
Kerper LE, Ballatori N, Clarkson TW (1992) Methylmercury transport across the blood-brain barrier by an amino acid carrier. Am J Physiol 262:R761–R765
Kinter WB, Pritchard JB (1977) Altered permeability of cell membranes. In:DHK See (ed) Handbook of physiology—reactions to environmental agents. American Physiol Society, Baltimore, MD, pp 563–576
Knauf PA, Rothstein A (1971) Effects of sulfhydryl and amino reactive reagents on anion and cation permeability of the human red blood cell. J Gen Physiol 58:190–210
Kone BC, Kaleta M, Gullens SR (1988) Silver ion (Ag+)-induced increases in cell membrane K+ and Na+ permeability in the renal proximal tubule:reversal by thiol reagents. J Membr Biol 102:11–19
Kone BC, Brenner RM, Gullens SR (1990) Sulfhydryl-reactive heavy metals increase cell membrane K+ and Ca2+ transport in renal proximal tubule. J Membr Biol 113:1–12
Kong C-T, Yet S-F, Lever JE (1993) Cloning and expression of a mammalian Na+/amino acid cotransporter with sequence similarities to Na+/glucose cotransporters. J Biol Chem 268:1509–1512
Lambert IH, Kramhoft B, Hoffmann EK (1984) Effect of copper on volume regulation in Ehrlich ascites tumour cells. Mol Physiol 6:83–98
Loghman-Adham M (1992) Inhibition of renal Na+-Pi cotransporter by mercuric chloride:role of sulfhydryl groups. J Cell Biochem 49:199–207
Lou M, Garay R, Alda Torrubia JO (1991) Cadmium uptake through the anion exchanger in human red blood cells. J Physiol (Lond) 443:123–136
Madsen NB (1963) Mercaptide-forming agents. In:Hoschester RM, Quastell JH (eds) Metabolic inhibitors. Academic, New York
Magos L, Webb M (1980) The interactions of selenium with cadmium and mercury. CRC Critical Rev Toxicol 1–38
Martell AE (1981) Chemistry of carcinogenic metals. Environ Health Perspect 40:207–226
McArdle HF (1992) The transport of iron and copper across the cell membrane:different mechanisms for different metals? Proc Nutr Soc 51:199–209
Nachshen DA (1984) Selectivity of the Ca binding site in synaptosome Ca channels:inhibition of Ca influx by multivalent metal cations. J Gen Physiol 83:941–967
Nemeth EF, Scarpa A (1987) Rapid mobilization of cellular Ca2+ in bovine parathyroid cells evoked by extracellular divalent cations. J Biol Chem 262:5188–5196
Oehme FW (1978) Mechanisms of heavy metal inorganic toxicities. In:Oehme (ed) Toxicity of heavy metals in the environment. Dekker, New York, pp 69–85
Orion Research Inc (1970) Mercury by electrode. Orion Newslett 11:41–42
Ortiz DF, Kreppel L, Speiser DM, Scheel G, McDonald G, Ow DW (1992) Heavy metal tolerance in the fission yeast requires an ATP-binding cassette-type vacuolar membrane transporter. EMBO J 11:3491–3499
Percival SS, Harris ED (1990) Copper transport ceruloplasmin:characterization of the cellular uptake mechanism. Am J Physiol 258:C140–C146
Philipson KD (1985) Sodium-calcium exchange in plasma membrane vesicles. Annu Rev Physiol 47:561–571
Preston GM, Jung JS, Guggino WB, Agre P (1993) The mercury-sensitive residue at cysteine 189 in the CHIP28 water channel. J Biol Chem 268:17–20
Rabenstein DL, Fairhurst MT (1975) Nuclear magnetic resonance studies of the solution chemistry of metal complexes. XI. The binding of methylmercury by sulfhydryl-containing amino acids and by glutathione. J Am Chem Soc 97:2086–2092
Rothstein A (1970) Sulfhydryl groups in membrane structure and function. In:Bronner F, Kleinzeller A (eds) Current topics in membranes and transport. Academic, New York, pp 135–176
Rothstein A, Mack E (1991) Actions of mercurials on cell volume regulation of dissociated MDCK cells. Am J Physiol 260:C113–C121
Schaeffer JF, Preston RL, Curran PF (1973) Inhibition of amino acid transport in rabbit intestine by P-chloromercuriphenyl sulfonic acid. J Gen Physiol 672:131–146
Schatzmann HJ (1982) The plasma membrane calcium pump of erythrocytes and other animal cells. In:Carafoli E (ed) Membrane transport of calcium. Academic, New York, pp 41–108
Scholtz E, Zeiske W (1988) A novel synergistic stimulation of Na+-transport across frog skin (Xenopus laevis) by external Cd2+- and Ca2+-ions. Pflugers Arch 413:174–180
Schwartz JH, Flamenbaum W (1976) Heavy metal-induced alterations in ion transport by turtle urinary bladder. Am J Physiol 230:1582–1589
Sheets MF, Hanck DA (1992) Mechanisms of extracellular divalent and trivalent cation block of the sodium current in canine cardiac purkinje cells. J Physiol (Lond) 454:299–320
Sillen LG, Martell AE (1971) Stability constants of metal ion complexes. Chemical Society, Special publication no 25
Silver S, Nucifora G, Chu L, Misra TK (1989) Bacterial resistance ATPases:primary pumps for exporting toxic cations and anions. Trends Biochem Sci 14:76–80
Simons TJB (1986) The role of anion transport in the passive movement of lead across the human red cell membrane. J Physiol (Lond) 378:287–312
Simons, TJB (1991) Calcium-dependent zinc efflux in human red blood cells. J Membr Biol 123:73–82
Simons TJB, Pocock G (1987) Lead enters bovine adrenal medullary cells through calcium channels. J Neurochem 48:383–389
Skroch P, Buchman C, Karin M (1993) Regulation of human and yeast metallothionein gene transcription by heavy metal ions. Prog Clin Biol Res 380:113–128
Smith JB, Dwyer SD, Smith L (1989) Cadmium evokes inositol polyphosphate formation and calcium mobilization. J Biol Chem 264:7115–7118
Smith MW, Phelps PC, Trump BF (1991) Cytosolic Ca2+ deregulation and blebbing after HgCl2 injury to cultured rabbit proximal tubule cells as determined by digital imaging microscopy. Proc Natl Acad Sci USA 88:4926–4930
Smith RM, Martell AE (1976) Critical stability constants. Plenum, New York
Stirling CE (1975) Mercurial perturbation of brush border membrane permeability in rabbit ileum. J Membr Biol 23:33–56
Stockand J, Sultan A, Molony D, DuBose T Jr, Sansom S (1993) Interactions of cadmium and nickel with K channels of vascular smooth muscle. Toxicol Appl Pharmacol 121:30–35
Tanaka K, Sueda K, Onosaka S, Okahara K (1975) Fate of 109Cd-labeled metallothionein in rats. Toxicol Appl Pharmacol 33:258–266
Templeton DM, Cherian MG (1983) Cadmium and hypertension. TIPS Rev 4:501–503
Tomsig JL, Suszkiw JB (1990) Pb2+-induced secretion from bovine chromaffin cells:fura-2 as a probe for Pb2+. Am J Physiol 259:C762–C768
Verbost PM, Flik G, Pang PKT, Lock RAC, Bonga SEW (1989) Cadmium inhibition of the erythrocyte Ca2+ pump. J Biol Chem 264:5613–5615
Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J (1993) Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nature Genetics 3:7–13
Webb JL (1966) Mercurials. Enzyme and metabolic inhibitors, vol 2, chap 7. Academic, New York, p 729
Weed R, Eber J, Rothstein A (1962) Interaction of mercury with human erythrocytes. J Gen Physiol 45:395–410
Wetterhahn-Jennette K (1981) The role of metals in carcinogenesis:biochemistry and metabolism. Environ Health Perspect 40:233–252
Wilkinson DJ, Post MA, Venglarik C, Chang D, Dawson D (1993) Mercury blockade of thiazide-sensitive NaCl cotransport in flounder urinary bladder. Toxicol Appl Pharmacol 122:170–176
Zhang R, vanHoek AN, Biwersi J, Verkman AS (1993) A point mutation at cysteine 189 blocks the water permeability of rat kidney water channel CHIP28k. Biochemistry 32:2938–2941
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Dawson, D.C., Ballatori, N. (1995). Membrane Transporters as Sites of Action and Routes of Entry for Toxic Metals. In: Goyer, R.A., Cherian, M.G. (eds) Toxicology of Metals. Handbook of Experimental Pharmacology, vol 115. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79162-8_3
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DOI: https://doi.org/10.1007/978-3-642-79162-8_3
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