Premium
Contribution of cyclic nucleotide‐gated (CNG) cation channels to active ion absorption across primary rat alveolar epithelial cell monolayers (RAECM)
Author(s) -
Zhang L.Q.,
Borok Z.,
Crandall E.D.,
Kim K.J.
Publication year - 2007
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.21.5.a554
Subject(s) - amiloride , chemistry , epithelial sodium channel , pimozide , cyclic nucleotide gated ion channel , apical membrane , biophysics , ion channel , ion transporter , patch clamp , inhibitory postsynaptic potential , pharmacology , endocrinology , biochemistry , sodium , cyclic nucleotide , nucleotide , membrane , receptor , biology , organic chemistry , gene , dopamine , haloperidol
We investigated the contribution of CNG cation channels to active ion transport across RAECM. Short‐circuit current (Isc) and monolayer resistance (Rt) were monitored with and without addition of increasing concentrations of putative inhibitors for CNG channels, pimozide or dichlorobenzamil, to apical fluid of RAECM. Results showed that Isc decreases and Rt increases as inhibitor concentration increases. The maximal inhibition of Isc afforded by pimozide and dichlorobenzamil was ~30 and ~80%, respectively. The apparent half‐maximal concentration (IC50), where the inhibitory effects of each inhibitor reach 50% of the effective inhibition of Isc, was ~11 μM and <0.1 μM for pimozide and dichlorobenzamil, respectively. When amiloride (10 μM) was added apically after pimozide (20 μM), a marked further decrease in Isc (down to ~25% of control) was noted, suggesting that these two agents most likely inhibit different cation channels (e.g., ENaC vs CNG, respectively). By contrast, no further inhibition of Isc was noted when amiloride was added apically after dichlorobenzamil (10 μM), consistent with inhibition of both ENaC and CNG channels by dichlorobenzamil. Although the molecular identity of the CNG channels in alveolar epithelium remains to be determined, these data indicate that apical Na entry into alveolar epithelial cells is via both CNG channels and ENaC. (Support: NIH and Hastings Foundation.)