Saturday, October 12, 2024
10/12/2024
Project Summary Potassium (K+) homeostasis is critical for normal cardiovascular and neuromuscular function, and disturbances in K+ homeostasis (e.g., hyperkalemia) can lead to life-threatening cardiovascular events. Extracellular K+ homeostasis is maintained by renal and extrarenal mechanisms. The kidneys have a remarkable capacity to regulate K+ excretion to match K+ intake, playing the major role in maintaining chronic K+ balance. In addition, extrarenal tissues (mainly skeletal muscle, the major K+ store) provide K+ buffering capacity by shifting K+ between the extracellular and intracellular fluids. Furthermore, gut sensing of dietary K+ appears to generate signals for regulating renal K+ excretion and extrarenal K+ shift. Thus, extracellular K+ homeostasis involves multiple organs and tissues, their adaptation to dietary K+ intake, and crosstalk among them. Despite marked progress in this field in recent decades, many critical issues concerning K+ homeostatic mechanisms remain unresolved due to a lack of appropriate methodology. A main limitation in studies of extracellular K+ homeostasis is an inability to quantify K+ fluxes in vivo. Although previous studies quantified K+ fluxes using 86Rb, a radioactive tracer for K+, radioactivity exposure and short half-life of 86Rb have limited its use to in vitro studies. Stable isotopes of a wide range of elements have been used to quantify fluxes of various substrates or blood constituents in vivo. However, in spite of the existence of two stable isotopes of K+ in nature (39K, 93.3% and 41K, 6.7%), this approach has not been applied to the study of K+ homeostasis in vivo due to analytical limitations. Dr. John Higgins, a geochemist at Princeton University, developed analytical methods for determining the ratio of stable K+ isotopes (41K/39K) in natural samples using inductively coupled plasma mass spectrometry. This state-of-the-art technology provides the opportunity to determine K+ fluxes in vivo using stable isotopes (i.e., without using radioactive tracers). The objective of the current proposal is to develop and validate this new approach for estimating whole-body K+ fluxes in vivo and extend it to assess K+ transport activities in individual tissues. If successfully developed, these new cutting-edge approaches will open new doors to answering important questions and filling gaps in K+ homeostatic mechanisms in vivo. These stable isotope approaches will be highly innovative, as they allow whole-body and in vitro K+ flux analyses that were infeasible with any conventional approaches, including those with 86Rb.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
