Ontogeny of flow-stimulated potassium secretion in rabbit cortical collecting duct: functional and molecular aspects

Am J Physiol Renal Physiol. 2003 Oct;285(4):F629-39. doi: 10.1152/ajprenal.00191.2003. Epub 2003 Jun 24.


High urinary flow rates stimulate K secretion in the fully differentiated but not neonatal or weanling rabbit cortical collecting duct (CCD). Both small-conductance secretory K and high-conductance Ca2+/stretch-activated maxi-K channels have been identified in the apical membrane of the mature CCD by patch-clamp analysis. We reported that flow-stimulated net K secretion in the adult rabbit CCD is 1) blocked by TEA and charybdotoxin, inhibitors of intermediate- and high-conductance (maxi-K) Ca2+-activated K channels, and 2) associated with increases in net Na absorption and intracellular Ca2+ concentration ([Ca2+]i). The present study examined whether the absence of flow-stimulated K secretion early in life is due to a 1) limited flow-induced rise in net Na absorption and/or [Ca2+]i and/or 2) paucity of apical maxi-K channels. An approximately sixfold increase in tubular fluid flow rate in CCDs isolated from 4-wk-old rabbits and microperfused in vitro led to an increase in net Na absorption and [Ca2+]i, similar in magnitude to the response observed in 6-wk-old tubules, but it failed to generate an increase in net K secretion. By 5 wk of age, there was a small, but significant, flow-stimulated rise in net K secretion that increased further by 6 wk of life. Luminal perfusion with iberiotoxin blocked the flow stimulation of net K secretion in the adult CCD, confirming the identity of the maxi-K channel in this response. Maxi-K channel alpha-subunit message was consistently detected in single CCDs from animals >/=4 wk of age by RT-PCR. Indirect immunofluorescence microscopy using antibodies directed against the alpha-subunit revealed apical labeling of intercalated cells in cryosections from animals >/=5 wk of age; principal cell labeling was generally intracellular and punctate. We speculate that the postnatal appearance of flow-dependent K secretion is determined by the transcriptional/translational regulation of expression of maxi-K channels. Furthermore, our studies suggest a novel function for intercalated cells in mediating flow-stimulated K secretion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Absorption
  • Aging / physiology
  • Animals
  • Blotting, Western
  • Calcium / metabolism
  • Fluorescent Antibody Technique
  • In Vitro Techniques
  • Intracellular Membranes / metabolism
  • Kidney Cortex
  • Kidney Tubules, Collecting / metabolism*
  • Kidney Tubules, Proximal / metabolism
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Large-Conductance Calcium-Activated Potassium Channels
  • Osmolar Concentration
  • Peptides / pharmacology
  • Potassium / metabolism*
  • Potassium Channels / metabolism
  • Potassium Channels, Calcium-Activated / genetics
  • RNA, Messenger / metabolism
  • Rabbits
  • Renal Circulation / physiology*
  • Sodium / metabolism
  • Tissue Distribution


  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Large-Conductance Calcium-Activated Potassium Channels
  • Peptides
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • RNA, Messenger
  • iberiotoxin
  • Sodium
  • Potassium
  • Calcium