Intracellular pH in pheochromocytoma (PC12) cells was manipulated by ‘acid loading’ the cells and the effect of such a change on radioactive zinc uptake was studied. It was found that zinc uptake was stimulated in cells loaded with protons without causing any measurable change in the intracellular pH. To confirm our assumption that the proton flux due to zinc entry is too small to be measured, we calculated the pH change that one would expect because of zinc influx. The intrinsic buffer capacity of PC12 cells was determined to be 8.03 mM/pH unit and was used in these calculations. It was found that at the five-minute incubation, zinc uptake occurring under our experimental conditions could cause a pH change of 0.000277 pH units per minute (assuming a 1:2 zinc:proton stoichiometry). This study adds a new dimension towards understanding the role played by intracellular pH in causing zinc entry into cells.
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References
M. P. Cuajungco G. J. Lees (1997) ArticleTitleZinc metabolism in the brain:relevance to human neurodegenerative disorders Neurobiol Dis 4 137–169
Frederickson, C.J., Zeng, Y., Balaji, R. V., DeWitt, D., Prough, D., Li, Y., Sarvey, J., Hough, C., Fierke, C., Grafe, M., Zornow, M. 2002. Extracellular Exchangeable Zinc: What is physiological? Society for Neuroscience Abstracts:Online
R. D. Palmiter S. D. Findley (1995) ArticleTitleCloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc Embo J 14 639–649
L. A. Gaither D. J. Eide (2000) ArticleTitleFunctional expression of the human hZIP2 zinc transporter J. Biol. Chem 275 5560–5564
R. A. Colvin (1998) ArticleTitleCharacterization of a plasma membrane zinc transporter in rat brain Neurosci. Lett 247 147–150
C. W. MacDiarmid L. A. Gaither D. Eide (2000) ArticleTitleZinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae Embo J 19 2845–2855
L. A. Gaither D. J. Eide (2001) ArticleTitleThe human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells J. Biol. Chem 276 22258–22264
Y. Jia J. M. Jeng S. L. Sensi J. H. Weiss (2002) ArticleTitleZn2+ currents are mediated by calcium-permeable AMPA/kainate channels in cultured murine hippocampal neurones J. Physiol 543 35–48
R. A. Colvin N. Davis R. W. Nipper P. A. Carter (2000) ArticleTitleZinc transport in the brain: routes of zinc influx and efflux in neurons J. Nutr. 130 1484s–1487s
S. L. Sensi H. Z. Yin S. G. Carriedo S. S. Rao J. H. Weiss (1999) ArticleTitlePreferential Zn2 + influx through Ca2+ -permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production Proc. Natl. Acad. Sci. USA 96 2414–2419
R. A. Colvin N. Davis R. W. Nipper P. A. Carter (2000) ArticleTitleEvidence for a zinc/proton antiporter in rat brain Neurochem. Int 36 539–547
L. A. Okorokov T. V. Kulakovskaya L. P. Lichko E. V. Polorotova (1985) ArticleTitleH+/ion antiport as the principal mechanism of transport systems in the vacuolar membrane of the yeast Saccharomyces carlsbergensis FEBS Lett 192 303–306
R. A. Colvin (2002) ArticleTitlepH dependence and compartmentalization of zinc transported across plasma membrane of rat cortical neurons Am. J. Physiol Cell Physiol 282 C317–329
J. A. Thomas R. N. Buchsbaum A. Zimniak E. Racker (1979) ArticleTitleIntracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ Biochemistry 18 2210–2218 Occurrence Handle1:CAS:528:DyaE1MXktVajt7Y%3D Occurrence Handle36128
W. F. Boron P. De Weer (1976) ArticleTitleIntracellular pH transients in squid giant axons caused by CO2, NH3, and metabolic inhibitors J. Gen. Physiol 67 91–112
A. Roos W. F. Boron (1981) ArticleTitleIntracellular pH. Physiol. Rev 61 296–434
R. A. Colvin C. P. Fontaine M. Laskowski D. Thomas (2003) ArticleTitleZn2 + transporters and Zn2+ homeostasis in neurons Eur. J. Pharmacol 479 171–185
S. W. Suh J. W. Chen M. Motamedi B. Bell K. Listiak N. F. Pons G. Danscher C. J. Frederickson (2000) ArticleTitleEvidence that synaptically-released zinc contributes to neuronal injury after traumatic brain injury Brain Res 852 268–273
J. Y. Koh S. W. Suh B. J. Gwag Y. Y. He C. Y. Hsu D. W. Choi (1996) ArticleTitleThe role of zinc in selective neuronal death after transient global cerebral ischemia Science 272 1013–1016 Occurrence Handle1:CAS:528:DyaK28XjtVejsrw%3D Occurrence Handle8638123
S. L. Sensi D. Ton-That P. G. Sullivan E. A. Jonas K. R. Gee L. K. Kaczmarek J. H. Weiss (2003) ArticleTitleModulation of mitochondrial function by endogenous Zn2 + pools Proc Natl. Acad. Sci. USA 100 6157–6162
S. L. Sensi D. Ton-That J. H. Weiss (2002) ArticleTitleMitochondrial sequestration and Ca2+-dependent release of cytosolic Zn2+ loads in cortical neurons Neurobiol Dis 10 100–108
B. Ye W. Maret B. L. Vallee (2001) ArticleTitleZinc metallothionein imported into liver mitochondria modulates respiration Proc. Natl. Acad. Sci. USA 98 2317–2322
M. Hershfinkel A. Moran N. Grossman I. Sekler (2001) ArticleTitleA zinc-sensing receptor triggers the release of intracellular Ca2+ and regulates ion transport Proc. Natl. Acad. Sci. USA 98 11749–11754
C. J. Frederickson S. W. Suh J. Y. Koh Y. K. Cha R. B. Thompson C. J. LaBuda R. V. Balaji M. P. Cuajungco (2002) ArticleTitleDepletion of intracellular zinc from neurons by use of an extracellular chelator in vivo and in vitro J. Histochem. Cytochem 50 1659–1662
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Balaji, R.V., Colvin, R.A. A Proton-Dependent Zinc Uptake in PC12 Cells. Neurochem Res 30, 171–176 (2005). https://doi.org/10.1007/s11064-004-2438-6
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DOI: https://doi.org/10.1007/s11064-004-2438-6