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The role of ENaC and CNG‐channels in AFC following continuous isoproterenol treatment
Author(s) -
Pedersen Lene Rørholm Engelbrecht,
Müllertz Katrine,
Amtorp Ole,
Jonassen Thomas E.N.
Publication year - 2006
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.20.4.a746-a
Subject(s) - epithelial sodium channel , amiloride , chemistry , stimulation , endocrinology , medicine , cyclic nucleotide gated ion channel , sodium , sodium channel , agonist , diltiazem , isoprenaline , receptor , biochemistry , cyclic nucleotide , calcium , nucleotide , organic chemistry , gene
It is well described that ‐adrenoceptor stimulation increases alveolar fluid clearance (AFC) in vivo, yet the pathways of sodium transport after continuous β‐adrenoceptor stimulation are not as well described, even though stimulation of epithelial sodium channels (ENaC) have been suggested to play a central role. Rats were treated with the β‐agonist isoproterenol (200 ìg/kg/h sc) for three days. Vehicle treated rats were used as controls. Western blotting on whole lung homogenates showed that isoproterenol treatment increased the abundance of both the α‐ and β‐subunit of ENaC (2.23 ± 0.51 and 2.74 ± 0.55 of vehicle, resp), whereas the level of γ‐ENaC was unchanged (1,20 ± 0,17 of vehicle). In parallel groups, AFC over a 1‐hour period was determined in anesthetized artificially ventilated rats, by installing an isosmolar Ringer‐solution containing 125I‐marked albumin into the bronchial tree. The study showed that AFC was increased in isoproterenol treated rats (18,9% ± 1,4 % vs. 13,3 % ± 3,3 %). These AFC studies were repeated during condition where sodium transport though either ENaC or the cyclic nucleotide gated (CNG) channel were blocked by adding amiloride or l‐cis diltiazem respectively to the instillate. Amiloride caused a net decrease of ~8 % in AFC in both groups, yet the net decrease when adding l‐cis‐diltiazem was 11,7 % in isoproterenol treated rats and 5,3 % in the vehicle treated rats. The results suggest that the increase in AFC after continuous β‐agonist stimulation is due to an increase in sodium transport through the CNG‐channel, while sodium transport though ENaC, despite an up regulation of both the α‐ and β‐ENaC subunit, is unchanged. The project was supported by the Danish Heart Foundation