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

Eric B. Gonzales, Cathy L. Bell-Horner, Mohammed I. Dibas, Ren-Qi Huang, Glenn H. Dillon

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

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 GABAA 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 GABAA receptors.

Original languageEnglish
Pages (from-to)184-189
Number of pages6
JournalNeuroscience Letters
Volume431
Issue number2
DOIs
StatePublished - 31 Jan 2008

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GABA-A Receptors
Phenylalanine
Ligand-Gated Ion Channels
Mutation
Nicotinic Receptors

Keywords

  • Cl channel
  • Desensitization
  • GABA receptor
  • Ligand-gated ion channel

Cite this

Gonzales, Eric B. ; Bell-Horner, Cathy L. ; Dibas, Mohammed I. ; Huang, Ren-Qi ; Dillon, Glenn H. / Stoichiometric analysis of the TM2 6′ phenylalanine mutation on desensitization in α1β2 and α1β2γ2 GABAA receptors. In: Neuroscience Letters. 2008 ; Vol. 431, No. 2. pp. 184-189.
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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 GABAA 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 GABAA receptors.",
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Stoichiometric analysis of the TM2 6′ phenylalanine mutation on desensitization in α1β2 and α1β2γ2 GABAA receptors. / Gonzales, Eric B.; Bell-Horner, Cathy L.; Dibas, Mohammed I.; Huang, Ren-Qi; Dillon, Glenn H.

In: Neuroscience Letters, Vol. 431, No. 2, 31.01.2008, p. 184-189.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Stoichiometric analysis of the TM2 6′ phenylalanine mutation on desensitization in α1β2 and α1β2γ2 GABAA receptors

AU - Gonzales, Eric B.

AU - Bell-Horner, Cathy L.

AU - Dibas, Mohammed I.

AU - Huang, Ren-Qi

AU - Dillon, Glenn H.

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AB - 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 GABAA 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 GABAA receptors.

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