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Characterization of a novel splice variant of ? ENaC subunit in human lungs.

ABSTRACT: Salt absorption via apical epithelial sodium channels (ENaC) is a critical rate-limiting process in maintaining airway and lung lining fluid at the physiological level. ? ENaC (termed ?1 in this article) has been detected in human lung epithelial cells in addition to ?, ?, and ? subunits (Ji HL, Su XF, Kedar S, Li J, Barbry P, Smith PR, Matalon S, Benos DJ. J Biol Chem 281: 8233-8241, 2006; Nie HG, Chen L, Han DY, Li J, Song WF, Wei SP, Fang XH, Gu X, Matalon S, Ji HL, J Physiol 587: 2663-2676, 2009) and may contribute to the differences in the biophysical properties of amiloride-inhibitable cation channels in pulmonary epithelial cells. Here we cloned a splicing variant of the ?1 ENaC, namely, ?2 ENaC in human bronchoalveolar epithelial cells (16HBEo). ?2 ENaC possesses 66 extra amino acids attached to the distal amino terminal tail of the ?1 ENaC. ?2 ENaC was expressed in both alveolar type I and II cells of human lungs as revealed by in situ hybridization and real-time RT-PCR. To characterize the biophysical and pharmacological features of the splicing variant, we injected Xenopus oocytes with human ENaC cRNAs and measured whole cell and single channel currents of ?1??, ?2??, and ??? channels. Oocytes injected with ?2?? cRNAs exhibited whole cell currents significantly greater than those expressing ?1?? and ??? channels. Single channel activity, unitary conductance, and open probability of ?2?? channels were significantly greater compared with ?1?? and ??? channels. In addition, ?2?? and ?1?? channels displayed significant differences in apparent Na(+) affinity, dissociation constant for amiloride (K(i)(amil)), the EC(50) for capsazepine activation, and gating kinetics by protons. Channels comprising of this novel splice variant may contribute to the diversities of native epithelial Na(+) channels.

SUBMITTER: Zhao RZ

PROVIDER: S-EPMC3379047 | biostudies-other | 2012 Jun

REPOSITORIES: biostudies-other

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Characterization of a novel splice variant of δ ENaC subunit in human lungs.

Zhao Run-Zhen RZ Nie Hong-Guang HG Su Xue-Feng XF Han Dong-Yun DY Lee Andrew A Huang Yao Y Chang Yongchang Y Matalon Sadis S Ji Hong-Long HL

American journal of physiology. Lung cellular and molecular physiology 20120413 12

Salt absorption via apical epithelial sodium channels (ENaC) is a critical rate-limiting process in maintaining airway and lung lining fluid at the physiological level. δ ENaC (termed δ1 in this article) has been detected in human lung epithelial cells in addition to α, β, and γ subunits (Ji HL, Su XF, Kedar S, Li J, Barbry P, Smith PR, Matalon S, Benos DJ. J Biol Chem 281: 8233-8241, 2006; Nie HG, Chen L, Han DY, Li J, Song WF, Wei SP, Fang XH, Gu X, Matalon S, Ji HL, J Physiol 587: 2663-2676, ...[more]

PMID: 22505667

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Dataset Information

Characterization of a novel splice variant of ? ENaC subunit in human lungs.

Publications

Characterization of a novel splice variant of δ ENaC subunit in human lungs.

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