Cl-channel activation is necessary for stimulation of Na transport in adult alveolar epithelial cells

In this review, we discuss evidence that supports the hypothesis that adren ergic stimulation of transepithelial Na absorption across the alveolar epit helium occurs indirectly by activation of apical Cl channels, resulting in hyperpolarization and an increased driving force for Na uptake through amil oride-sensitive Na channels. This hypothesis differs from the prevailing id ea that adrenergic-receptor activation increases the open probability of Na channels, leading to an increase in apical membrane Na permeability and an increase in Na and fluid uptake from the alveolar space. We review results from cultured alveolar epithelial cell monolayer experiments that show inc reases in apical membrane Cl conductance in the absence of any change in Na conductance after stimulation by selective beta-adrenergic-receptor agonis ts. We also discuss possible reasons for differences in Na-channel regulati on in cells grown in monolayer culture compared with that in dissociated al veolar epithelial cells. Finally, we describe some preliminary in vivo data that suggest a role for Cl-channel activation in the process of amiloride- sensitive alveolar fluid absorption.