Picrotoxin-mediated antagonism of α3β4 and α7 acetylcholine receptors

• Published in: Neuroreport Vol. 15; no. 12; pp. 1969 - 1973
• Main Authors: Erkkila, Brian E, Weiss, David S, Wotring, Virginia E
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 26-08-2004; Lippincott Williams and Wilkins
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Vertebrates: nervous system and sense organs; Rat; Rodentia; Glycine; Vertebrata; Cholinergic receptor; Mammalia; Animal; α7 nicotinic receptor; Neurotransmitter; GABA; α3 nicotinic receptor; Acetylcholine; Nicotinic receptor; Biological receptor
• ISSN: 0959-4965; 1473-558X
• DOI: 10.1097/00001756-200408260-00027

Picrotoxin (PTX) is a convulsant that antagonizes many inhibitory ligand-gated receptors. The mechanism of PTX block is believed to involve residues which line the pore in the second transmembrane domain (M2). The α3β4 and α7 nicotinic acetylcholine receptors (nAChRs) have high homology to inhibitory LGICs in this M2 region and therefore could also be susceptible to block by PTX. Here, we report that PTX is an effective inhibitor at these nicotinic receptors (rat), with IC50 values of 96.1±5.5 and 194.9±19.2 μM for the α3β4 and α7, respectively. These results provide insights into the structure-function relation of PTX-mediated antagonism in this family of ligand-activated receptors. Furthermore they should also be considered when employing PTX to selectively eliminate GABA- or glycine-mediated events.