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Departments of 1 Anesthesiology, 2 Physiology and Biophysics, and 3 Comparative Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35249
Existing evidence supports the presence
of active transport of Na+ across the mammalian alveolar
epithelium and its upregulation by agents that increase cytoplasmic
cAMP levels. However, there is controversy regarding the mechanisms
responsible for this upregulation. Herein we present the results of
various patch-clamp studies indicating the presence of 25- to 27-pS,
amiloride-sensitive, moderately selective Na+ channels
(Na+-to-K+ permeability ratio = 7:1) located on
the apical membranes of rat alveolar type II (ATII) cells maintained in
primary culture. The addition of terbutaline to the bath solution
increased the open probability of single channels present in
cell-attached patches of ATII cells without affecting their
conductance. A similar increase in open probability was seen after the
addition of protein kinase A, ATP, and Mg2+ to the
cytoplasmic side of inside-out patches. Measurement of short-circuit
currents across confluent monolayers of rat or rabbit ATII cells
indicates that terbutaline and 8-(4-chlorophenylthio)-cAMP increase vectorial Na+ transport and activate
Cl
channels. Currently, there is a controversy as to
whether the cAMP-induced increase in Na+ transport is due
solely to hyperpolarization of the cytoplasmic side of the ATII cell
membrane due to Cl influx or whether it results from
simultaneous stimulation of both Cl and
Na+ conductive pathways. Additional studies are needed to
resolve this issue.
terbutaline; adenosine 3',5'-cyclic monophosphate; alveolar type II cells; sodium channels; amiloride; patch clamp; 5-(N-ethyl-N-isopropyl)-amiloride
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