title: An unexpected journey: conceptual evolution of mechanoregulated potassium transport in the distal nephron.
abstract: Flow-induced K secretion (FIKS) in the aldosterone-sensitive distal nephron (ASDN) is mediated by large-conductance, Ca(2+)/stretch-activated BK channels composed of pore-forming α-subunits (BKα) and accessory β-subunits. This channel also plays a critical role in the renal adaptation to dietary K loading. Within the ASDN, the cortical collecting duct (CCD) is a major site for the final renal regulation of K homeostasis. Principal cells in the ASDN possess a single apical cilium whereas the surfaces of adjacent intercalated cells, devoid of cilia, are decorated with abundant microvilli and microplicae. Increases in tubular (urinary) flow rate, induced by volume expansion, diuretics, or a high K diet, subject CCD cells to hydrodynamic forces (fluid shear stress, circumferential stretch, and drag/torque on apical cilia and presumably microvilli/microplicae) that are transduced into increases in principal (PC) and intercalated (IC) cell cytoplasmic Ca(2+) concentration that activate apical voltage-, stretch- and Ca(2+)-activated BK channels, which mediate FIKS. This review summarizes studies by ourselves and others that have led to the evolving picture that the BK channel is localized in a macromolecular complex at the apical membrane, composed of mechanosensitive apical Ca(2+) channels and a variety of kinases/phosphatases as well as other signaling molecules anchored to the cytoskeleton, and that an increase in tubular fluid flow rate leads to IC- and PC-specific responses determined, in large part, by the cell-specific composition of the BK channels.
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Rolando
authors.initials: R
authors.lastname: Carrisoza-Gaytan
authors.affiliation: Renal-Electrolyte Division, Department of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Marcelo D
authors.initials: MD
authors.lastname: Carattino
authors.affiliation: Renal-Electrolyte Division, Department of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kleyman
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York; and lisa.satlin@mssm.edu.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Satlin
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D006801:Humans; D015640:Ion Channel Gating; D017136:Ion Transport; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D008564:Membrane Potentials; D009399:Nephrons / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D000450:Aldosterone; D011188:Potassium
keywords: WNK kinases; cilia; kidney; mechanoregulation; potassium transport