Comparison of two types of δENaC channels cloned from human lungs

Abstract

δENaC has been detected in human lung epithelial cells. Here we cloned a splicing variant, namely, δ2ENaC in human bronchoalveolar epithelial cells. δ2ENaC possesses 66 extra amino acids attached to the distal amino terminal tail of the δ1ENaC. δ2ENaC was expressed in both alveolar type I and II cells as revealed by in situ hybridization. To compare the biophysical and pharmacological features of the splicing variant with the δ1βγ channels, we examined the whole‐cell and single channel properties comparing with those of δ1βγ and αβγ channels. Divergent from δ1βγ channels, the macroscopic currents of δ2βγ channels were greater; the apparent Na+ affinity was stronger; the apparent dissociation constant for amiloride (Kiamil) but not Evans blue was smaller; the EC50 value of capsazepine activation was less; and the gating kinetics by protons were markedly faster. The single channel activity, unitary conductance, and open probability of δ2βγ channels were significantly greater compared to δ1βγ channels. The potential longevity of δ2βγ at cell surface, as shown by the faster exocytosis and slower endocytosis could contribute to the enhanced channel activity. Our data demonstrate that the channels composed of the splicing variant segregated from both δ1βγ and αβγ channels by strikingly diverse biophysical/pharmacological properties and regulation by physiological signal. Our results may account for the heterogeneities of native amiloride‐sensitive cation channels in human lung and other epithelial tissues. This work was supported by NIH grants HL87017, HL031197, ES015676, ES017218, and National Natural Science Foundation of China (30971181).