A distinct contribution of the delta subunit to acetylcholine receptor channel activation revealed by mutations of the M2 segment

Biophysical Journal
J Chen, A Auerbach

Abstract

Acetylcholine receptor (AChR) channels with proline (P) mutations in the putative pore-forming domain (at the 12' position of the M2 segment) were examined at the single-channel level. For all subunits (alpha, beta, epsilon, and delta), a 12'P mutation increased the open channel lifetime >5-fold. To facilitate the estimation of binding and gating rate constants, subunits with 12'P mutations were co-expressed with alpha subunits having a binding site mutation that slows channel opening (alphaD200N). In these AChRs, a 12'P mutation in epsilon or beta slowed the closing rate constant approximately 6-fold but had no effect on either the channel opening rate constant or the equilibrium dissociation constant for ACh (Kd). In contrast, a 12'P mutation in delta slowed the channel closing rate constant only approximately 2-fold and significantly increased both the channel opening rate constant and the Kd. Pairwise expression of 12'P subunits indicates that mutations in epsilon and beta act nearly independently, but one in delta reduces the effect of a homologous mutation in epsilon or beta. The results suggest that a 12'P mutation in epsilon and beta has mainly local effects, whereas one in delta has both local and distributed effects t...Continue Reading

References

Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Feb 1, 1995·Biophysical Journal·D J MaconochieJ H Steinbach

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Citations

Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·M ZhouA Auerbach
Aug 30, 2000·The Journal of General Physiology·C GrosmanA Auerbach
Jun 5, 2008·Molecular Pharmacology·Julius MilitanteJoe Henry Steinbach
Feb 16, 2011·Biophysical Journal·Shaweta Gupta, Anthony Auerbach
Dec 18, 1998·Neuron·J P Changeux, S J Edelstein

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