Stoichiometric analysis of the TM2 6' phenylalanine mutation on desensitization in alpha1beta2 and alpha1beta2gamma2 GABA A receptors.
The presence of phenylalanine (F) at the 6' position of transmembrane domain 2 (TM2) in the alpha4 subunit of alpha4beta2 nicotinic receptors enhances desensitization. As the GABA A receptor affords the ability to study the influence of as few as one and as many as five Fs at this position, we have used it to investigate potential subunit- and stoichiometry-dependent effects of the TM2 6'F mutation on desensitization. Whereas the presence of one F at this position decreased extent of desensitization, desensitization was increased in all configurations that included two or more Fs at the TM2 6' position; desensitization was particularly rapid with 3 or 4 F residues present. Our results demonstrate the ability of F residues at the TM2 6' position to modulate desensitization is likely conserved in the cys-loop family of ligand-gated ion channels. Moreover, our findings demonstrate both stoichiometric- and subunit-dependent effects of the ability of this mutation to regulate desensitization in GABA A receptors.
Gonzales
Eric B
EB
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, United States.
Bell-Horner
Cathy L
CL
Dibas
Mohammed I
MI
Huang
Ren-Qi
RQ
Dillon
Glenn H
GH
D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009154:Mutation / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010649:Phenylalanine / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D013269:Stochastic Processes; D014162:Transfection / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D021122:Protein Subunits; D011963:Receptors, GABA-A; D010649:Phenylalanine; D005680:gamma-Aminobutyric Acid