Mechanisms of increased Na+ transport in ATII cells by cAMP: we agree to disagree and do more experiments

Existing evidence supports the presence of active transport of Na+ across t he mammalian alveolar epithelium and its upregulation by agents that increa se cytoplasmic cAMP levels. However, there is controversy regarding the mec hanisms responsible for this upregulation. Herein we present the results of various patch-clamp studies indicating the presence of 25- to 27-pS, amilo ride-sensitive, moderately selective Na+ channels (Na+-to-K+ permeability r atio = 7:1) located on the apical membranes of rat alveolar type II (ATII) cells maintained in primary culture. The addition of terbutaline to the bat h solution increased the open probability of single channels present in; ce ll-attached patches of ATII cells without affecting their conductance. A si milar increase in open probability was seen after the addition of protein k inase A, ATP, and Mg2+ to the cytoplasmic side of inside-out patches. Measu rement of short-circuit currents across confluent monolayers of rat or rabb it ATII cells indicates that terbutaline and 8-(4-chlorophenylthio)-cAMP in crease vectorial Na+ transport and activate Cl- channels. Currently, there is a controversy as to whether the cAMP-induced increase in Na+ transport i s due solely to hyperpolarization of the cytoplasmic side of the ATII cell membrane due to Cl- influx or whether it results from simultaneous stimulat ion of both Cl- and Na+ conductive pathways. Additional studies are needed to resolve this issue.