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Up‐Regulation of Heterologously Expressed αβγ ENaC Channel Activity by Nitric Oxide in Tissue Culture Medium
Author(s) -
JI HONGLONG,
Nie Hongguang,
Su XueFeng,
Smith Peter R
Publication year - 2008
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.22.1_supplement.932.1
Subject(s) - epithelial sodium channel , amiloride , nitric oxide , chemistry , ion channel , in vitro , in vivo , ion transporter , superoxide , biophysics , microbiology and biotechnology , pharmacology , sodium , biochemistry , biology , receptor , membrane , enzyme , organic chemistry
Several groups have demonstrated that nitric oxide (NO) reduces the activity of native amiloride‐sensitive sodium channels (ENaC) and αβγ ENaC channels heterologously expressed in oocytes. However, conflicting results for the effects of NO on the biological function of cells have been observed between in vivo and in vitro studies due to the superoxide‐dependent consumption of NO in biological media ( Keynes RG et al. 2003 ). We aimed to study the regulation of ENaC by NO under physiological conditions by applying DetaNONOate in a tissue culture medium (L‐15). The activity of αβγ ENaC channels was recorded using the two‐electrode voltage clamp techniques. Our results showed that when added to L‐15 culture medium, NO increased αβγ ENaC activity. In contrast, NO decreased αβγ ENaC activity when added to a saline medium (OR‐2), consistent with other report ( DuVall MD et al. 1998 ). Coexpression of CFTR did not affect the opposite effects of NO exposure on αβγ ENaC activity. These results indicate that NO can regulate transepithelial ion transport in a medium‐dependent pattern. Our results suggest a novel mechanism for the regulation of apical ion transport by NO in vivo . Furthermore, our data provide an explanation why NO inhibits ENaC and alveolar fluid clearance in vitro but gaseous NO inhalation is still being used clinically to prevent and treat pulmonary edema. Supported by: NIH HL 87017 and AHA 555333B