Dietary potassium loads call on intercalated cell PIEZO1 to go with the flow

Adult humans in steady-state excrete ∼90% of dietary K+ via the kidney's connecting segment and cortical collecting duct. Baseline renal K+ secretion is mediated by the principal cell (PC) ROMK K+ channel in a manner sustained by active ENaC-mediated, amiloride-sensitive Na+ reabsorption (Figure 1). 1 Carrisoza-Gaytan R. Mutchler S.M. Carattino F. et al. PIEZO1 is a distal nephron mechanosensor and is required for flow-induced K+ secretion. J Clin Invest. Mar 1 2024; : 134https://doi.org/10.1172/JCI174806 Crossref Scopus (2) Google Scholar ,2 Carrisoza-Gaytan R. Carattino M.D. Kleyman T.R. Satlin L.M. An unexpected journey: conceptual evolution of mechanoregulated potassium transport in the distal nephron. Am J Physiol Cell Physiol. Feb 15 2016; 310: C243-C259https://doi.org/10.1152/ajpcell.00328.2015 Crossref PubMed Scopus (41) Google Scholar The transition to a high K+ (HiK) diet increases renal tubular flow rates, leading to an amiloride-insensitive increase in renal K+ secretion within less than a day. In rabbit kidney, amiloride-insensitive renal K+ excretion develops only after weaning. Similar adaptation is reflected in human ROMK-deficient Type II Bartter syndrome, characterized by post-natal severe hyperkalemia that can transition in later infancy to mild, manageable hypokalemia. This developmentally regulated amiloride-insensitive component of renal K+ secretion is mediated by the large conductance SLO1/BK K+ channel of collecting duct. In adult mice, HiK upregulates both ROMK and BK channels, but only the former is aldosterone-dependent. 2 Carrisoza-Gaytan R. Carattino M.D. Kleyman T.R. Satlin L.M. An unexpected journey: conceptual evolution of mechanoregulated potassium transport in the distal nephron. Am J Physiol Cell Physiol. Feb 15 2016; 310: C243-C259https://doi.org/10.1152/ajpcell.00328.2015 Crossref PubMed Scopus (41) Google Scholar