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Nat Commun. 2014 Jun 3;5:3948. doi: 10.1038/ncomms4948.

Physiological sodium concentrations enhance the iodide affinity of the Na+/I- symporter.

Author information

  • 11] Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA [2].
  • 2Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
  • 3Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.

Abstract

The Na(+)/I(-) symporter (NIS) mediates active I(-) transport--the first step in thyroid hormonogenesis--with a 2Na(+):1I(-) stoichiometry. NIS-mediated (131)I(-) treatment of thyroid cancer post-thyroidectomy is the most effective targeted internal radiation cancer treatment available. Here to uncover mechanistic information on NIS, we use statistical thermodynamics to obtain Kds and estimate the relative populations of the different NIS species during Na(+)/anion binding and transport. We show that, although the affinity of NIS for I(-) is low (Kd=224 μM), it increases when Na(+) is bound (Kd=22.4 μM). However, this Kd is still much higher than the submicromolar physiological I(-) concentration. To overcome this, NIS takes advantage of the extracellular Na(+) concentration and the pronounced increase in its own affinity for I(-) and for the second Na(+) elicited by binding of the first. Thus, at physiological Na(+) concentrations, ~79% of NIS molecules are occupied by two Na(+) ions and ready to bind and transport I(-).

PMID:
24888603
PMCID:
PMC4248369
DOI:
10.1038/ncomms4948
[PubMed - indexed for MEDLINE]
Free PMC Article
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