| First Author | Shi S | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 305 |
| Issue | 11 | Pages | F1585-92 |
| PubMed ID | 24107424 | Mgi Jnum | J:202944 |
| Mgi Id | MGI:5523400 | Doi | 10.1152/ajprenal.00337.2013 |
| Citation | Shi S, et al. (2013) Gamma subunit second transmembrane domain contributes to epithelial sodium channel gating and amiloride block. Am J Physiol Renal Physiol 305(11):F1585-92 |
| abstractText | The epithelial sodium channel (ENaC) is comprised of three homologous subunits. Channels composed solely of alpha- and beta-subunits (alphabeta-channels) exhibit a very high open probability (Po) and reduced sensitivity to amiloride, in contrast to channels composed of alpha- and gamma-subunits or of all three subunits (i.e., alphagamma- and alphabetagamma-channels). A mutant channel comprised of alpha- and beta-subunits, and a chimeric gamma-subunit where the region immediately preceding (beta12 and wrist) and encompassing the second transmembrane domain (TM2) was replaced with the corresponding region of the beta-subunit (gamma-betaTM2), displayed characteristics reminiscent of alphabeta-channels, including a reduced amiloride potency of block and a loss of Na(+) self-inhibition (reflecting an increased Po). Substitutions at key pore-lining residues of the gamma-betaTM2 chimera enhanced the Na(+) self-inhibition response, whereas key gamma-subunit substitutions reduced the response. Furthermore, multiple sites within the TM2 domain of the gamma-subunit were required to confer high amiloride potency. In summary, we have identified novel pore-lining residues of the gamma-subunit of ENaC that are important for proper channel gating and its interaction with amiloride. |
