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Modulation of CFTR function by reactive oxygen‐nitrogen species
Author(s) -
Denny Sarah,
Lazrak Ahmed,
Noah James W,
Noah Diana L,
Matalon Sadis
Publication year - 2009
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.23.1_supplement.999.2
Subject(s) - chemistry , forskolin , cystic fibrosis transmembrane conductance regulator , intracellular , glutathione , reactive oxygen species , chloride channel , biophysics , extracellular , activator (genetics) , nitric oxide , biochemistry , medicine , endocrinology , biology , enzyme , receptor , organic chemistry , gene
We examined the effects of Reactive Oxygen‐Nitrogen Species (RONS) on chloride (Cl − ) currents across Xenopus oocytes heterologously expressing the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), using the two micro‐electrode voltage clamp method. The baseline current value was 310 ± 73 nA (mean ± SE, n = 5). Addition of 10μM Forskolin (an adenylate cyclase activator) activated CFTR and raised the current to 4750 ± 904 nA (mean ± SE, n = 5). Following this activation, the addition of 1mM 3‐morpholinosydnominine (SIN‐1), which generates both superoxide and nitric oxide, along with 10µM Forskolin, resulted in a total inhibition of the Cl − current within 10 minutes to its pre‐activation level. The SIN‐1 mediated decrease in CFTR current was totally absent when SIN‐1 was allowed to decompose to its stable form, SIN‐1c, prior to treatment. Interestingly, the SIN‐1 effect was blocked by intracellular but not extracellular addition of 1mM glutathione (GSH), a RONS scavenger. We conclude that exposure of oocytes expressing CFTR channels to RONS causes a decrease in the Cl − current via an unknown mechanism, potentially involving intracellular pathways that are inhibited by GSH.