Neuromuscular acetylcholine receptors (AChRs) are ion channels that alternatively adopt stable conformations that either allow (open) or prohibit (closed) ionic conduction. We probed the dynamics of pore (M2) residues at the diliganded gating transition state by using single-channel kinetic and rate-equilibrium free energy relationship (Φ-value) analyses of mutant AChRs. The mutations were at the equatorial (9′) position of the α, β, and ε subunits (n = 15) or at sites between the equator and the extracellular domain in the α-subunit (n = 8), We also studied AChRs having only one of the two α-subunits mutated. The results indicate that the α-subunit, like the δ-subunit, has a region of flexure near the middle of M2, that the two α-subunits experience distinct energy barriers to gating at the equator (but not else-where), and that the collective subunit motions at the equator are asymmetric during the AChR gating isomerization.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Oct 18 2005|
- Ion channels
- Rate-equilibrium free energy relationship (REFER) analysis
ASJC Scopus subject areas