Cytosolic Ca(2+)-induced modulation of ion selectivity and amiloride sensitivity of a cation channel and beta agonist action in fetal lung epithelium.
The cytosolic Ca2+ concentration ([Ca2+]i) affects many cell functions, including the modulation of ion channel activity. In this study patch clamp experiments using primary cultures of fetal distal lung epithelium (FDLE) demonstrated that the elevation of [Ca2+]i modulated a 25pS amiloride-blockable non selective cation (NSC) channel's ion selectivity and sensitivity to amiloride. An elevation of [Ca2+]i from 0.1 microM to 1mM both increased open probability (Po) and decreased the ratio of the permeability to Na to the permeability to K (PNa/PK) from 1.96 +/- 0.11 (SEM, n = 6) to 0.88 +/- 0.04 (n = 6). Within the range of [Ca2+]i from 0.1 microM to 100 microM amiloride (0.5 microM) decreased Po, however amiloride (0.5 microM) no longer affected Po of the NSC channel when [Ca2+]i was increased to 1mM under physiologic membrane potentials. A beta adrenergic agonist (terbutaline, 10 microM) increased Po in cell-attached patches from almost 0 (Po less than 0.01; n = 9) to 0.39 +/- 0.09 (n = 9) and [Ca2+]i from 40 +/- 6nM (n = 9) to more than 1 microM. This suggested that amiloride-blockable NSC channel activity and ion permeability are modulated by changes in [Ca2+]i near physiologic membrane potentials and a beta adrenergic agonist increases [Ca2+]i to more than 1 microM (unlike other epithelial including adult alveolar cells) which is associated with activation the NSC channel.
Marunaka
Y
Y
Division of Respiratory Research, Hospital for Sick Children Research Institute, University of Toronto, Ontario, Canada.
Tohda
H
H
Hagiwara
N
N
O'Brodovich
H
H
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002412:Cations; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D008564:Membrane Potentials; D010539:Permeability; D051381:Rats; D013726:Terbutaline / Q000494:pharmacology
D002412:Cations; D005456:Fluorescent Dyes; D007473:Ion Channels; D000584:Amiloride; D013726:Terbutaline; D002118:Calcium; D016257:Fura-2