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

Juan P. Nicola, Nancy Carrasco, L. Mario Amzel

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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 K d s 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 =224μM), it increases when Na+ is bound (K d =22.4μM). However, this K d 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-.

Original languageEnglish (US)
Article number3948
JournalNature communications
Volume5
DOIs
StatePublished - Jun 3 2014
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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