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. 1993 Dec 15;90(24):11806–11810. doi: 10.1073/pnas.90.24.11806

Zinc modulation of a transient potassium current and histochemical localization of the metal in neurons of the suprachiasmatic nucleus.

R C Huang 1, Y W Peng 1, K W Yau 1
PMCID: PMC48073  PMID: 8265630

Abstract

The effect of Zn2+ on a voltage-dependent, transient potassium current (IA) in acutely dissociated neurons from the suprachiasmatic nucleus was studied with the whole-cell patch-clamp technique. At micromolar concentrations, Zn2+ markedly potentiated IA activated from a holding potential of -60 mV, which is the resting potential of these neurons. This potentiation occurred at a Zn2+ concentration as low as 2 microM and increased with higher Zn2+ concentrations. The Zn2+ action appears to arise from a shift in the steady-state inactivation of IA to more positive voltages. At 30 microM, Zn2+ shifted the half-inactivation voltage by +20 mV (from -80 mV to -60 mV), and 200 microM Zn2+ shifted this voltage by +45 mV (from -80 mV to -35 mV). Histochemically, we have also observed Zn2+ staining throughout the suprachiasmatic nucleus; the staining is particularly intense in the ventrolateral region of the nucleus, which receives the major fiber inputs. Our findings suggest that Zn2+, presumably synaptically released, may modulate the electrical activity of suprachiasmatic nucleus neurons through IA. Because vesicular Zn2+ is fairly widespread in the central nervous system, it is conceivable that this kind of Zn2+ modulation on IA, and possibly on other voltage-activated currents, exists elsewhere in the brain.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Assaf S. Y., Chung S. H. Release of endogenous Zn2+ from brain tissue during activity. Nature. 1984 Apr 19;308(5961):734–736. doi: 10.1038/308734a0. [DOI] [PubMed] [Google Scholar]
  2. Connor J. A., Stevens C. F. Voltage clamp studies of a transient outward membrane current in gastropod neural somata. J Physiol. 1971 Feb;213(1):21–30. doi: 10.1113/jphysiol.1971.sp009365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Crawford I. L., Connor J. D. Localization and release of glutamic acid in relation to the hippocampal mossy fibre pathway. Nature. 1973 Aug 17;244(5416):442–443. doi: 10.1038/244442a0. [DOI] [PubMed] [Google Scholar]
  4. Danscher G. Exogenous selenium in the brain. A histochemical technique for light and electron microscopical localization of catalytic selenium bonds. Histochemistry. 1982;76(3):281–293. doi: 10.1007/BF00543951. [DOI] [PubMed] [Google Scholar]
  5. Frederickson C. J. Neurobiology of zinc and zinc-containing neurons. Int Rev Neurobiol. 1989;31:145–238. doi: 10.1016/s0074-7742(08)60279-2. [DOI] [PubMed] [Google Scholar]
  6. Gilly W. F., Armstrong C. M. Divalent cations and the activation kinetics of potassium channels in squid giant axons. J Gen Physiol. 1982 Jun;79(6):965–996. doi: 10.1085/jgp.79.6.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gilly W. F., Armstrong C. M. Slowing of sodium channel opening kinetics in squid axon by extracellular zinc. J Gen Physiol. 1982 Jun;79(6):935–964. doi: 10.1085/jgp.79.6.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  9. Harrison N. L., Radke H. K., Talukder G., Ffrench-Mullen J. M. Zinc modulates transient outward current gating in hippocampal neurons. Receptors Channels. 1993;1(2):153–163. [PubMed] [Google Scholar]
  10. Howell G. A., Welch M. G., Frederickson C. J. Stimulation-induced uptake and release of zinc in hippocampal slices. Nature. 1984 Apr 19;308(5961):736–738. doi: 10.1038/308736a0. [DOI] [PubMed] [Google Scholar]
  11. Huang R. C. Sodium and calcium currents in acutely dissociated neurons from rat suprachiasmatic nucleus. J Neurophysiol. 1993 Oct;70(4):1692–1703. doi: 10.1152/jn.1993.70.4.1692. [DOI] [PubMed] [Google Scholar]
  12. Ibata Y., Otsuka N. Electron microscopic demonstration of zinc in the hippocampal formation using Timm's sulfide silver technique. J Histochem Cytochem. 1969 Mar;17(3):171–175. doi: 10.1177/17.3.171. [DOI] [PubMed] [Google Scholar]
  13. Ito C., Wakamori M., Akaike N. Dual effect of glycine on isolated rat suprachiasmatic neurons. Am J Physiol. 1991 Feb;260(2 Pt 1):C213–C218. doi: 10.1152/ajpcell.1991.260.2.C213. [DOI] [PubMed] [Google Scholar]
  14. Müller T. H., Misgeld U., Swandulla D. Ionic currents in cultured rat hypothalamic neurones. J Physiol. 1992 May;450:341–362. doi: 10.1113/jphysiol.1992.sp019130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Neher E. Two fast transient current components during voltage clamp on snail neurons. J Gen Physiol. 1971 Jul;58(1):36–53. doi: 10.1085/jgp.58.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Peters S., Koh J., Choi D. W. Zinc selectively blocks the action of N-methyl-D-aspartate on cortical neurons. Science. 1987 May 1;236(4801):589–593. doi: 10.1126/science.2883728. [DOI] [PubMed] [Google Scholar]
  17. Pérez-Clausell J., Danscher G. Intravesicular localization of zinc in rat telencephalic boutons. A histochemical study. Brain Res. 1985 Jun 24;337(1):91–98. doi: 10.1016/0006-8993(85)91612-9. [DOI] [PubMed] [Google Scholar]
  18. Romans A. Y., Graichen M. E., Lochmüller C. H., Henkens R. W. Kinetics and mechanism of dissociation of zinc ion from carbonic anhydrase. Bioinorg Chem. 1978 Sep;9(3):217–229. doi: 10.1016/s0006-3061(78)80007-6. [DOI] [PubMed] [Google Scholar]
  19. Rudy B. Diversity and ubiquity of K channels. Neuroscience. 1988 Jun;25(3):729–749. doi: 10.1016/0306-4522(88)90033-4. [DOI] [PubMed] [Google Scholar]
  20. Slomianka L., Danscher G., Frederickson C. J. Labeling of the neurons of origin of zinc-containing pathways by intraperitoneal injections of sodium selenite. Neuroscience. 1990;38(3):843–854. doi: 10.1016/0306-4522(90)90076-g. [DOI] [PubMed] [Google Scholar]
  21. Spires S., Begenisich T. Chemical properties of the divalent cation binding site on potassium channels. J Gen Physiol. 1992 Aug;100(2):181–193. doi: 10.1085/jgp.100.2.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Stanfield P. R. The effect of zinc ions on the gating of the delayed potassium conductance of frog sartorius muscle. J Physiol. 1975 Oct;251(3):711–735. doi: 10.1113/jphysiol.1975.sp011118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Van den Pol A. N. The hypothalamic suprachiasmatic nucleus of rat: intrinsic anatomy. J Comp Neurol. 1980 Jun 15;191(4):661–702. doi: 10.1002/cne.901910410. [DOI] [PubMed] [Google Scholar]
  24. Westbrook G. L., Mayer M. L. Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons. Nature. 1987 Aug 13;328(6131):640–643. doi: 10.1038/328640a0. [DOI] [PubMed] [Google Scholar]
  25. Wheal H. V., Thomson A. M. The electrical properties of neurones of the rat suprachiasmatic nucleus recorded intracellularly in vitro. Neuroscience. 1984 Sep;13(1):97–104. doi: 10.1016/0306-4522(84)90262-8. [DOI] [PubMed] [Google Scholar]
  26. Xie X. M., Smart T. G. A physiological role for endogenous zinc in rat hippocampal synaptic neurotransmission. Nature. 1991 Feb 7;349(6309):521–524. doi: 10.1038/349521a0. [DOI] [PubMed] [Google Scholar]

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