Premium
Pannexin‐1 Channel Activity and Associated ATP Release in Podocytes in Response to Adipokines
Author(s) -
Li Guangbi,
Zhang Qinghua,
Li Ningjun,
Ritter Joseph K.,
Li PinLan
Publication year - 2017
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.31.1_supplement.991.9
Subject(s) - pannexin , adipokine , inflammation , carbenoxolone , medicine , chemistry , endocrinology , gap junction , microbiology and biotechnology , biology , connexin , intracellular , leptin , obesity
Pannexin‐1 (PANX1) channel has been reported to mediate the release of ATP that is involved in local tissue inflammation, obesity, and many chronic degenerative diseases. It remains unknown whether PANX1 channel is present in podocytes and thereby mediates ATP release leading to glomerular inflammation or fibrosis. In the present study, we characterized the PANX1 channel in podocytes and examined the possibility of this channel in mediating ATP release induced by adipokines. By real time RT‐PCR, Western blot analysis and immunohistochemistry, we demonstrated that among 3 different pannexins, PANX1 is mostly enriched in podocytes either cultured or in situ in mouse glomeruli. Using patch clamp technique, we recorded a large voltage‐gated outward current under the Cs + in /Na + out gradient, which was 290.2±8.7 pA at +80 mV. Na‐gluconate or Na‐asparate substitution for NaCl in the bath solution blocked voltage‐gated outward currents and shifted the reversal potential of PANX1 currents to right, indicating the anion permeability of this channel. Pharmacologically, the recorded voltage‐gated outward currents were substantially attenuate by either carbenoxolone (CBX) or probenecid (PBNC), the specific PANX1 channel inhibitors (to 23.8±2.5% and 21.4±1.7% of control, respectively). Given the stimulatory role of extracellular ATP in inflammation and chronic low‐grade inflammation as a hallmark of obesity, we tested whether adipokines from fat cells activate PANX1 channel activity to release ATP. Adipokine, visfatin was shown to remarkably enhance pannexin‐1 channel activity in podocytes (to 252.5±7.7% of control), which was completely abolished by CBX. However, another adipokine, adiponectin significantly blocked pannexin‐1 channel activity to 29.9±4.4% of control, a level similar to the effects of CBX and PBNC. Correspondingly, visfatin significantly increased ATP release from podocytes by almost 2 folds, which was prevented by CBX, PBNC or adiponectin. These results suggest that PANX1 functions as an anion channel in podocytes to control ATP release, which is regulated by adipokines. Support or Funding Information This study is supported by NIH grants DK54927, DK102539, HL057244, HL075316, and HL122937.