Stable potassium isotopes (41K/39K) track transcellular and paracellular potassium transport in biological systems

John A. Higgins, Danielle Santiago Ramos, Stefania Gili, Cornelia Spetea, Scott Kanoski, Darren Ha, Alicia A. McDonough, Jang H. Youn

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4 Scopus citations


As the most abundant cation in archaeal, bacterial, and eukaryotic cells, potassium (K+) is an essential element for life. While much is known about the machinery of transcellular and paracellular K transport–channels, pumps, co-transporters, and tight-junction proteins—many quantitative aspects of K homeostasis in biological systems remain poorly constrained. Here we present measurements of the stable isotope ratios of potassium (41K/39K) in three biological systems (algae, fish, and mammals). When considered in the context of our current understanding of plausible mechanisms of K isotope fractionation and K+ transport in these biological systems, our results provide evidence that the fractionation of K isotopes depends on transport pathway and transmembrane transport machinery. Specifically, we find that passive transport of K+ down its electrochemical potential through channels and pores in tight-junctions at favors 39K, a result which we attribute to a kinetic isotope effect associated with dehydration and/or size selectivity at the channel/pore entrance. In contrast, we find that transport of K+ against its electrochemical gradient via pumps and co-transporters is associated with less/no isotopic fractionation, a result that we attribute to small equilibrium isotope effects that are expressed in pumps/co-transporters due to their slower turnover rate and the relatively long residence time of K+ in the ion pocket. These results indicate that stable K isotopes may be able to provide quantitative constraints on transporter-specific K+ fluxes (e.g., the fraction of K efflux from a tissue by channels vs. co-transporters) and how these fluxes change in different physiological states. In addition, precise determination of K isotope effects associated with K+ transport via channels, pumps, and co-transporters may provide unique constraints on the mechanisms of K transport that could be tested with steered molecular dynamic simulations.

Original languageEnglish (US)
Article number1016242
JournalFrontiers in Physiology
StatePublished - Oct 26 2022

All Science Journal Classification (ASJC) codes

  • Physiology (medical)
  • Physiology


  • Na-K ATPase
  • homeostasis
  • physiology
  • potassium
  • potassium channel
  • stable isotope


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