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Pannexin1 is a novel renal ATP release mechanism
Author(s) -
Hanner Fiona,
PetiPeterdi Janos
Publication year - 2010
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.24.1_supplement.606.27
Subject(s) - nephron , reabsorption , purinergic receptor , chemistry , probenecid , gap junction , connexin , microbiology and biotechnology , intracellular , medicine , adenosine , endocrinology , biochemistry , biology , renal function , sodium , organic chemistry
Purinergic signaling regulates key functions of the renal tubules, including salt and water transport. Due to ectonucleotidase activity along the nephron, it has been suggested that ATP is locally released by tubular cells. Previously, we have shown that the gap junction protein connexin 30 (Cx30) plays a role in ATP release and purinergic mediation of salt reabsorption in the distal nephron/collecting duct. A new candidate for ATP transport is the pannexin1 hemichannel (Px1) which is sensitive to mechanical stress, allows the passage of ATP and unlike Cxs, is insensitive to [Ca 2+ ] e . Therefore we tested the hypothesis that Px1 hemichannels may also mediate ATP release in the distal nephron. Using immunofluorescence, we observed Px1 in the distal convoluted tubules, thin limbs, and select cells of the cortical collecting duct. Px1 function was tested using a luciferase‐based ATP assay and a dye uptake assay in two renal epithelial cell types that endogenously express Px1: MDCK and M1. Px1 was inhibited with either probenecid or Px1 siRNA. Probenecid significantly inhibited ATP release in both M1 (by ~60%) and MDCK (by ~40%) cell types, while Px1 siRNA significantly reduced ATP release in MDCK cells only (by ~30%). Both treatments failed to significantly alter dye uptake in either cell type. Based on these results, we concluded that Px1 is co‐expressed with other Cx isoforms and may regulate ATP release in the distal nephron.