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This Article Full Text Full Text (PDF) All Versions of this Article: 577/2/569    most recent jphysiol.2006.120287v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sedelnikova, A. Articles by Weiss, D. S. Search for Related Content PubMed PubMed Citation Articles by Sedelnikova, A. Articles by Weiss, D. S. Related Collections Neuroscience

¹ Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
² Department of Neurobiology, UAB School of Medicine, Birmingham, AL 35294, USA
³ Solae, St Louis, MO 63102, USA

Picrotoxin, a potent antagonist of the inhibitory central nervous system GABA_A and glycine receptors, is believed to interact with residues that line the central ion pore. These pore-lining residues are in the second transmembrane domain (TM2) of each of the five constituent subunits. One of these amino acids, a threonine at the 6' location, when mutated to phenylalanine, abolishes picrotoxin sensitivity. It has been suggested that this threonine, via hydrogen bonding, directly interacts with the picrotoxin molecule. We previously demonstrated that this mutation, in the , or subunit, can impart picrotoxin resistance to the GABA receptor. Since the functional pentameric GABA receptor contains two subunits, two subunits and one subunit, it is not clear how many and subunits must carry this mutation to impart the resistant phenotype. In this study, by coexpression of mutant or subunits with their wild-type counterparts in various defined ratios, we demonstrate that any single subunit carrying the 6' mutation imparts picrotoxin resistance. Implications of this finding in terms of the mechanism of antagonism are considered.

(Received 1 September 2006; accepted after revision 18 September 2006; first published online 21 September 2006)
Corresponding author D. S. Weiss: Department of Physiology, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Email: weissd{at}uthscsa.edu

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