Stoichiometric analysis of the TM2 6′ phenylalanine mutation on desensitization in α1β2 and α1β2γ2 GABAA receptors

• DOI: 10.1016/j.neulet.2007.11.039
• Publication Date: 2007-12-04T14:18:41Z
• Authors: Eric B. Gonzales; Cathy L. Bell-Horner; Mohammed I. Dibas; Ren-Qi Huang; Glenn H. Dillon
• Keywords: 0301 basic medicine; 03 medical and health sciences

Abstract The presence of phenylalanine (F) at the 6′ position of transmembrane domain 2 (TM2) in the α4 subunit of α4β2 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.