Amiloride-blockable Ca2+-activated Na+-permeant channels in the fetal distal lung epithelium

Abstract

The Na+ transport function of alveolar epithelium represents an important mechanism for clearance of fluid in air space at birth. I observed the activity of two types of amiloride-blockable Na+-permeant cation channels in the apical membrane of fetal distal lung epithelium cultured on permeable filters for 2 days after harvesting of the cells from Wistar rats of 20 days gestation (term = 22 days). One type was a nonselective cation (NSC) channel and had a linear current/voltage (I/V) relationship with a single-channel conductance of 26.9 +/- 0.8 pS (n = 5). The other type was highly Na+ selective (i.e. Na+ channel) and had an inwardly rectifying I/V relationship with a single-channel conductance of 11.8 +/- 0.2 pS (n = 5) around resting membrane potential. The NSC channel was more frequently observed (1.37 +/- 0.15 per patch membrane; n = 73) than the Na+ channel (0.15 +/- 0.40 per patch membrane; n = 73). However, the open probability of the NSC channel was smaller than that of the Na+ channel. Both types of the channels were activated by cytosolic Ca2+, however the sensitivity to cytosolic Ca2+ was much higher in the Na+ channel than in the NSC channel. Furthermore, both types of the channels were blocked by amiloride or benzamil. The half-maximal inhibitory concentration (IC50) of amiloride or benzamil of the Na+ channel was 1-2 microM, while that of NSC channel was less than 1 microM. Both channels were activated by insulin.