Biophysical features of a new cloned delta ENaC subunit

The epithelial sodium channels (ENaC) is the critical rate‐limiting determinant in maintaining airway and lung lining fluid. δ ENaC (δ 1 ) has been detected in human lung epithelial cells in addition to α, β, and γ subunits. Here we cloned a splicing variance of δ 1 counterpart, termed as δ 2 ENaC, in human bronchial epithelial cell line 16HBE140. Compared with δ 1 subunit, δ 2 ENaC possesses 66 extra amino acid residues in its cytosolic amino terminal tail. To characterize the biophysical and pharmacological features of the δ 2 ENaC, we comparably examined the whole‐cell and single channel properties associated with δ 1 βγ and δ 2 βγ hENaC expressed in Xenopus oocytes. The relative cation selectivity ratio of Na + /Li + /K + (1/0.69/0.09) for δ 2 βγ ENaC was similar with that of δ 1 βγ ENaC (1/0.64/0.07). And there was no significant difference in external Na + affinity between δ 1 βγ and δ 2 βγ hENaC. The apparent dissociation constant for amiloride ( K i amil ), EC 50 value of capsazepine, proton gating kinetics for δ 2 βγ ENaC, however, significantly differed from those of δ 1 βγ ENaC. Single‐channel patch clamp results revealed that unitary conductance, single channel activity ( NP o ), and gating kinetics varied between δ 1 βγ and δ 2 βγ ENaC. Our data demonstrate that heterologously expressed δ 1 and δ 2 ENaC channels are segregated by their biophysical and pharmacological properties, at least partially accounting for the diverse native epithelial Na + channels in lung epithelial cells. Supported by HL087017 and HL095435.