Patch clamp experiments on nicotinic acetylcholine receptor-ion channels in bullforg sympathetic ganglion cells

1989 ◽  
Vol 414 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Kenji Kuba ◽  
Eiichiro Tanaka ◽  
Eiichi Kumamoto ◽  
Shoichi Minota
Keyword(s):  
Ion Channels ◽  
Patch Clamp ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Sympathetic Ganglion ◽  
Ganglion Cells ◽  
Nicotinic Acetylcholine

The α7 Nicotinic Acetylcholine Receptor Subunit Exists in Two Isoforms that Contribute to Functional Ligand-Gated Ion Channels

2004 ◽  
Vol 66 (3) ◽  
pp. 420-429 ◽  
Author(s):  
Emily G. Severance ◽  
Hongling Zhang ◽  
Yolmari Cruz ◽  
Sergei Pakhlevaniants ◽  
Stephen H. Hadley ◽  
...  
Keyword(s):  
Ion Channels ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Receptor Subunit ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Gated Ion Channels ◽  
Ligand Gated Ion Channels

scholarly journals Discovery of peptide ligands through docking and virtual screening at nicotinic acetylcholine receptor homology models

2017 ◽  
Vol 114 (38) ◽  
pp. E8100-E8109 ◽  
Author(s):  
Abba E. Leffler ◽  
Alexander Kuryatov ◽  
Henry A. Zebroski ◽  
Susan R. Powell ◽  
Petr Filipenko ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Critical Role ◽  
Nicotinic Acetylcholine ◽  
Docking Algorithm ◽  
Addiction Therapy ◽  
Peptide Toxins ◽  
Homology Models

Venom peptide toxins such as conotoxins play a critical role in the characterization of nicotinic acetylcholine receptor (nAChR) structure and function and have potential as nervous system therapeutics as well. However, the lack of solved structures of conotoxins bound to nAChRs and the large size of these peptides are barriers to their computational docking and design. We addressed these challenges in the context of the α4β2 nAChR, a widespread ligand-gated ion channel in the brain and a target for nicotine addiction therapy, and the 19-residue conotoxin α-GID that antagonizes it. We developed a docking algorithm, ToxDock, which used ensemble-docking and extensive conformational sampling to dock α-GID and its analogs to an α4β2 nAChR homology model. Experimental testing demonstrated that a virtual screen with ToxDock correctly identified three bioactive α-GID mutants (α-GID[A10V], α-GID[V13I], and α-GID[V13Y]) and one inactive variant (α-GID[A10Q]). Two mutants, α-GID[A10V] and α-GID[V13Y], had substantially reduced potency at the human α7 nAChR relative to α-GID, a desirable feature for α-GID analogs. The general usefulness of the docking algorithm was highlighted by redocking of peptide toxins to two ion channels and a binding protein in which the peptide toxins successfully reverted back to near-native crystallographic poses after being perturbed. Our results demonstrate that ToxDock can overcome two fundamental challenges of docking large toxin peptides to ion channel homology models, as exemplified by the α-GID:α4β2 nAChR complex, and is extendable to other toxin peptides and ion channels. ToxDock is freely available atrosie.rosettacommons.org/tox_dock.

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