Non-transferrin-bound iron uptake by rat liver. Role of membrane potential difference

T. L. Wright, J. G. Fitz, R. A. Weisiger

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Abstract

Non-transferrin-bound iron is efficiently cleared from serum by the liver and may be primarily responsible for the hepatic damage seen in iron-overload states. We tested the hypothesis that transport of ionic iron is driven by the negative electrical potential difference across the liver cell membrane. Extraction of 55Fe-labeled ferrous iron (1 μM) from Krebs bicarbonate buffer by the perfused rat liver was continuously monitored as the transmembrane potential difference (measured using conventional microelectrodes) was altered over the physiologic range by isosmotic ion substitution. Resting membrane potential in Krebs bicarbonate buffer was -28 ± 1 mV. Perfusion with 1 μM ferrous iron caused a reversible 3 ± 1 mV depolarization, and higher concentrations of iron caused even greater depolarization. Conversely, depolarization of the liver cells consistently reduced iron extraction. Replacement of sodium with potassium (70 mM) or choline (131 mM) depolarized the hepatocytes to -15 and -20 mV and decreased iron extraction by 28 and 31%, respectively. Perfusion with bicarbonate free-solutions containing tricine buffer (10 mM) reduced the membrane potential to -23 mV and reduced iron extraction by 18%. In contrast, the high basal extraction of iron (91.1 ± 1.4%) was not further increased by substitution of nitrate for chloride (-46 mV) or infusion of glucagon (-34 mV). All effects were reversible, suggesting that perfusion with 1 μM iron produced little toxicity. These findings are consistent with an electrogenic transport mechanism for uptake of non-transferrin-bound iron that is driven by the transmembrane potential difference.

Original languageEnglish (US)
Pages (from-to)1842-1847
Number of pages6
JournalJournal of Biological Chemistry
Volume263
Issue number4
StatePublished - 1988

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Liver
Membrane Potentials
Rats
Iron
Membranes
Bicarbonates
Depolarization
Buffers
Perfusion
Substitution reactions
Iron Overload
Microelectrodes
Choline
Glucagon
Cell membranes
Nitrates
Chlorides
Hepatocytes
Potassium
Toxicity

ASJC Scopus subject areas

  • Biochemistry

Cite this

Non-transferrin-bound iron uptake by rat liver. Role of membrane potential difference. / Wright, T. L.; Fitz, J. G.; Weisiger, R. A.

In: Journal of Biological Chemistry, Vol. 263, No. 4, 1988, p. 1842-1847.

Research output: Contribution to journalArticle

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