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A New Stable Isotope Method for Quantifying Potassium Distribution and Fluxes In Vivo
Author(s) -
Youn Jang,
Oh Young Taek,
Ramos Danielle,
Gili Stefania,
McDonough Alicia,
Higgins John
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02499
Subject(s) - in vivo , chemistry , isotope , stable isotope ratio , isotopes of potassium , centrifugation , potassium , chromatography , biology , physics , microbiology and biotechnology , organic chemistry , quantum mechanics
The potassium (K + ) gradient across a cell membrane is a critical determinant of membrane potential. Thus, disturbances in K + homeostasis, which involve both renal and extrarenal mechanisms, can provoke life‐threatening cardiovascular events. We know that K + traverses membranes through channels, co‐transporters, and ATPases, but determining mechanisms controlling fluxes between extracellular and intracellular compartments in vivo is hampered by a lack of appropriate methods to quantify K + fluxes in vivo , particularly those into and out of cells. Objective and Hypothesis : The objective of this study was to implement stable K + isotopes to quantify K + fluxes in vivo . 41 K and 39 K are stable isotopes of K + with 39 K roughly 14‐fold more abundant than 41 K. We tested the hypothesis that the 41 K/ 39 K ratio in rat plasma in vivo is altered by intravenous 41 K infusion, and that these changes can be analyzed to quantify K + distribution and fluxes. Methods: 41 K (as KCl) was infused (0.5 mg 41 K / h) for 1 h into tail vein of male Wistar rats (~300 g body weight; n = 4), and blood was sampled from tail artery before, during, and after the 41 K infusion. Plasma was obtained by centrifugation, and 41 K/ 39 K ratio measured using inductively coupled plasma mass spectrometry. Results: The plasma 41 K/ 39 K ratio increased during the 1‐h 41 K infusion and decreased upon cessation of the infusion (Figure 1; data expressed as change from the baseline, d 41 K/ 39 K) whereas the concentration of total K + in plasma (i.e., 41 K + 39 K) was not significantly increased by the 41 K infusion (data not shown). The time course of d 41 K/ 39 K was analyzed using a 2‐compartmental (2‐C) model of K + distribution and elimination, including the extracellular (ECF, compartment 1) and the intracellular (ICF, compartment 2) fluid K + pools, K + fluxes between the pools, and renal K + excretion (Figure 2). We assume ECF is instantly equilibrated with plasma. The model fit the data (Figure 1), and model parameters were robustly identified (V 1 [volume of ECF] = 29.6 ± 3.6 ml; k 01 = 0.012 ± 0.003 min ‐1 ; k 21 = 0.13 ± 0.02 min ‐1 ; and k 12 = 0.012 ± 0.001 min ‐1 ). Conclusions: This novel approach using stable isotopes can quantify K + distribution and fluxes in vivo and can be implemented to identify mechanisms in (patho)physiological regulation of potassium homeostasis.