Properties of a novel GABAA receptor γ2 subunit mutation associated with seizures

Journal of Pharmacological Sciences

Volumn 121, Issue 1, 2013, Pages 84-87

  Migita, Keisuke ^a   Yamada, Junko ^a   Nikaido, Yoshikazu ^a   Shi, Xiu Yu ^b,c   Kaneko, Sunao ^a   Hirose, Shinichi ^b   Ueno, Shinya ^a  

^a HIROSAKI UNIVERSITY   (Japan)

^b FUKUOKA UNIVERSITY   (Japan)

^c CHINESE PLA GENERAL HOSPITAL   (China)

Author keywords

Epilepsy

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR GAMMA2; ASPARAGINE; BICUCULLINE; BICUCULLINE METHIODIDE; DIAZEPAM; SERINE; TAU PROTEIN; TAU1 PROTEIN; TAU2 PROTEIN; UNCLASSIFIED DRUG; ZINC; ZINC CHLORIDE; 4 AMINOBUTYRIC ACID A RECEPTOR;

ARTICLE; CHANNEL GATING; CONCENTRATION RESPONSE; EMBRYO; EVOKED RESPONSE; GABAERGIC SYSTEM; GENE ACTIVATION; GENE INACTIVATION; GENETIC ASSOCIATION; HUMAN; HUMAN CELL; INHIBITION KINETICS; MISSENSE MUTATION; MUTATIONAL ANALYSIS; PATCH CLAMP; PH; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SUBUNIT; RECEPTOR POTENTIAL; SEIZURE; WHOLE CELL; WILD TYPE; EPILEPSY; GENETICS; METABOLISM;

EPILEPSY; HUMANS; MUTATION, MISSENSE; PATCH-CLAMP TECHNIQUES; RECEPTORS, GABA-A;

MLCS; MLOWN;

EID: 84873849182     PISSN: 13478613     EISSN: 13478648     Source Type: Journal    
DOI: 10.1254/jphs.12222SC     Document Type: Article

References (15)

1. Barnard EA, Skolnick P, Olsen RW, Mohler H, Sieghart W, Biggio G, et al. International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acid A receptors: classification on the basis of subunit structure and receptor function. Pharmacol Rev. 1998;50:291-313.
2. Bonnert TP, McKernan RM, Farrar S, le Bourdellès B, Heavens RP, Smith DW, et al. Theta, a novel γ-aminobutyric acid type A receptor subunit. Proc Natl Acad Sci U S A. 1999;96:9891-9896.
3. Sieghart W, Sperk G. Subunit composition, distribution and function of GABAA receptor subtypes. Curr Top Med Chem. 2002;2:795-816.
4. Hirose S. A new paradigm of channelopathy in epilepsy syndromes: intracellular trafficking abnormality of channel molecules. Epilepsy Res. 2006;70:S206-S217.
5. Bowser DN, Wagner DA, Czajkowski C, Cromer BA, Parker MW, Wallace RH, et al. Altered kinetics and benzodiazepine sensitivity of a GABAA receptor subunit mutation [γ2(R43Q)] found in human epilepsy. Proc Natl Acad Sci U S A. 2002;99: 15170-15175.
6. Baulac S, Huberfeld G, Gourfinkel-An I, Mitropoulou G, Beranger A, Prud'homme JF, et al. First genetic evidence of GABAA receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene. Nat Genet. 2001;28:46-48.
7. Shi X, Huang MC, Ishii A, Yoshida S, Okada M, Morita K, et al. Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies. J Hum Genet. 2010;55:375-378.
8. Migita K, Haines WR, Voigt MM, Egan TM. Polar residues of the second transmembrane domain influence cation permeability of the ATP-gated P2X2 receptor. J Biol Chem. 2001;276: 30934-30941.
9. Sigel E, Buhr A. The benzodiazepine binding site of GABAA receptors. Trends Pharmacol Sci. 1997;18:425-429.
10. Boileau AJ, Li T, Benkwitz C, Czajkowski C, Pearce RA. Effects of gamma2S subunit incorporation on GABAA receptor macroscopic kinetics. Neuropharmacology. 2003;44:1003-1012.
11. Mercik K, Pytel M, Cherubini E, Mozrzymas JW. Effect of extracellular pH on recombinant α1β2γ2 and α1β2 GABAA receptors. Neuropharmacology. 2006;51:305-314.
12. Wagner DA, Czajkowski C. Structure and dynamics of the GABA binding pocket: a narrowing cleft that constricts during activation. J Neurosci. 2001;21:67-74.
13. Colquhoun D. Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors. Br J Pharmacol. 1998;125: 924-947.
14. Feng HJ, Kang JQ, Song L, Dibbens L, Mulley J, Macdonald RL. Delta subunit susceptibility variants E177A and R220H associated with complex epilepsy alter channel gating and surface expression of alpha4beta2delta GABAA receptors. J Neurosci. 2006;26:1499-1506.
15. Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982;157:105-132.