Cellular effects ofβ-adrenergic and of cAMP stimulation on potassium transport in rat alveolar epithelium

Abstract

Alveolar fluid absorption is greatly enhanced by cAMP and by β-adrenergic agonists via an increase in Na⁺ transport. Little is known about K⁺ homeostasis under these circumstances. We studied K⁺ transport across alveolar epithelium in isolated perfused rat lungs stimulated either by dibutyryl-cAMP or isoproterenol. K⁺ fluxes and the apparent permeability of⁸⁶Rb across the epithelium (alveoli to plasma) were interpreted according to a model involving two types of cells, B and L, distinguished by the location of Na⁺−K⁺-ATPases (basal and luminal). Water is considered to be absorbed by B cells in a solute-coupled process energized by a basolateral Na⁺−K⁺-ATPase that is stimulated by isoproterenol and cAMP. K⁺ transport out of the alveoli is due to the activity of a Na⁺−K⁺-ATPase located in the apical membrane of L cells. In the present study net transport rate of K⁺ was −0.5±0.15 nmol/s,n=20 (out of alveoli) in control conditions. When the epithelium was stimulated by dibutyryl-cAMP (10⁻⁴ mol/l) net absorption of K⁺ reversed to net ‘secretion’ into alveoli (3.2±0.31 nmol/s), fluid absorption was not stimulated. K⁺ ‘secretion’ was abolished by apical Ba²⁺, indicating it was due to opening of apical K⁺ channels. Basolateral ouabain reversed net K⁺ ‘secretion’ to net absorption indicating that K⁺ entry into alveoli was dependent on activity of B cell basolateral Na⁺−K⁺-ATPase (masking simultaneous K⁺ removal by apical L cell Na⁺−K⁺-pump). When larger concentrations of dibutyryl-cAMP (10⁻³ mol/l) or when isoproterenol were used to stimulate the epithelium there was a tripling of fluid absorption. In this situation a biphasic response of K⁺ transport was observed. Initially, net K⁺ influx similar to that observed in 10⁻⁴ mol/l dibutyryl-cAMP experiments occurred, followed by a large K⁺ efflux from alveolar spaces. This may reflect stimulation of apical Na⁺−K⁺-ATPase in L cells, combined with partial closure of apical K⁺ channels in B cells. The variations of the apparent permeability of⁸⁶Rb, measured from alveoli to plasma, reinforce this interpretation of the mechanisms of K⁺ transport. Our results suggest that K⁺ transport across alveolar epithelium is modulated by isoproterenol and cAMP, by stimulation of Na⁺−K⁺-ATPase in B and L cells supplemented by control of K⁺ channels.