Cl- regulation of a Ca (2+) -activated nonselective cation channel in beta-agonist-treated fetal distal lung epithelium
Tohda, H.; Foskett, J.K.; O'Brodovich, H.; Marunaka, Y.
American Journal of Physiology 266(1 Pt 1): C104-C109
1994
ISSN/ISBN: 0002-9513 PMID: 7508184 Document Number: 423111
Nonselective cation (NSC) channels have been identified in the apical membrane of fetal distal lung epithelium (FDLE). However, their physiological role in Na+ transport is uncertain. Because terbutaline, a beta-2-agonist, increases Na+ transport by FDLE, we studied its effect and selected signal transduction mechanisms on NSC channel activity. Using patch-clamp and single-cell imaging techniques, we found that terbutaline activated the NSC channel by 1) increasing its sensitivity to cytosolic Ca-2+ concentration ((Ca-2+)-c) by 100- to 1,000-fold, 2) increasing (Ca-2+)-c from 35 nM to 3.3 mu-M, 3) producing a dependency of the NSC channel activity on the cytosolic Cl- concentration ((Cl-)-c) at a physiological (Ca-2+)-c, and 4) inducing a reduction in the (Cl-)-c from 45 to 25 mM, which directly activates the beta-2-treated NSC channel. These observations indicate that a beta-2-agonist physiologically activates an amiloride-blockable NSC channel in FDLE through an increase in its sensitivity to (Ca-2+)-c, resulting in the development of a (Cl-)-c dependency at a physiological (Ca-2+)-c associated with both an increase in (Ca-2+)-c and a reduction in (Cl-)-c. A development of the (Cl-)-c dependency and a reduction in (Cl-)-c act as a second messenger of the beta-agonist signal transduction pathway in this Na+-transporting epithelium.