Additive stimulatory effect of extracellular calcium and potassium on non-transferrin ferric iron uptake by HeLa and K562 cells.
We studied the effects of Ca(2+) and K(+) on non-transferrin iron uptake from ferric citrate complex by HeLa and K562 cells. Uptake experiments in Na-HEPES buffer (137 mM NaCl, 4 mM KCl) showed that extracellular Ca(2+) stimulated the iron uptake. The rate of iron uptake in 4 mM Ca(2+) was about 3-5 times higher than without Ca(2+). The iron uptake in K-HEPES buffer (68 mM NaCl, 75 mM KCl) with a high K(+) level was transiently stimulated during the first 10 min. The rate of iron uptake for 0.4 mM Ca(2+) was approximately 3 times higher in K-HEPES buffer than in Na-HEPES buffer. The calcium channel blockers verapamil (50 microM) and nifedipine (5 microM) had no effect on the uptake either in control Na-HEPES buffer or after K(+) stimulation in K-HEPES buffer. The sodium channel blocker lidocaine (50 microM) also had no effect on the uptake of iron in Na-HEPES buffer as well as after K(+) stimulation. Furthermore, the iron uptake was not significantly affected when Na(+) in the Na-HEPES and K-HEPES buffers was replaced by isotonic saccharose. We conclude that extracellular calcium per se, and not intracellular calcium or Ca(2+) transport, stimulates ferric iron uptake by both HeLa and K562 cells. A high level of extracellular K(+) also stimulates the uptake, probably via cell membrane depolarization. Na(+) is not involved in these stimulations of iron uptake. The transient K(+) effect and continuous Ca(2+) effect seem to be additive.
Musílková
J
J
Cell Growth Control Laboratory, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic.
Kovár
J
J
D001692:Biological Transport; D002021:Buffers; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D005290:Ferric Compounds / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation
D002021:Buffers; D002121:Calcium Channel Blockers; D005290:Ferric Compounds; D000001:Calcimycin; C025314:ferric citrate; D008012:Lidocaine; D007501:Iron; D018021:Lithium Chloride; D011188:Potassium; D002118:Calcium