Abstract

The specific aims are to determine: 1) the biophysical properties of native GABA receptors (GABARs) from identified CNS neurons. Single channel properties will be characterized and a kinetic gating scheme developed for GABARs from each neuronal type; 2) the pharmacological regulation of native GABARs from identified CNS neurons; 3) the functional expression of recombinant GABAR subtypes into GABAR isoforms; 4) the biophysical properties of recombinant GABAR isoforms assembled from GABAR subtypes which have been shown to be coassembled in hippocampal dentate granule cells, pyramidal neurons, cerebellar granule cells, and Purkinje cells; 5) the pharmacological regulation of these.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS033300-04
Application #
2703044
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Baughman, Robert W
Project Start
1995-05-01
Project End
1999-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Neurology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Lagrange, Andre H; Hu, NingNing; Macdonald, Robert L (2018) GABA beyond the synapse: defining the subtype-specific pharmacodynamics of non-synaptic GABAA receptors. J Physiol 596:4475-4495
Wang, Chen-Hung; Hernandez, Ciria C; Wu, Junyi et al. (2018) A Missense Mutation A384P Associated with Human Hyperekplexia Reveals a Desensitization Site of Glycine Receptors. J Neurosci 38:2818-2831
Hernandez, Ciria C; Kong, Weijing; Hu, Ningning et al. (2017) Altered Channel Conductance States and Gating of GABAA Receptors by a Pore Mutation Linked to Dravet Syndrome. eNeuro 4:
Ishii, Atsushi; Kang, Jing-Qiong; Schornak, Cara C et al. (2017) A de novo missense mutation of GABRB2 causes early myoclonic encephalopathy. J Med Genet 54:202-211
Shen, Dingding; Hernandez, Ciria C; Shen, Wangzhen et al. (2017) De novo GABRG2 mutations associated with epileptic encephalopathies. Brain 140:49-67
Kang, Jing-Qiong; Macdonald, Robert L (2016) Molecular Pathogenic Basis for GABRG2 Mutations Associated With a Spectrum of Epilepsy Syndromes, From Generalized Absence Epilepsy to Dravet Syndrome. JAMA Neurol 73:1009-16
Hernandez, Ciria C; Klassen, Tara L; Jackson, Laurel G et al. (2016) Deleterious Rare Variants Reveal Risk for Loss of GABAA Receptor Function in Patients with Genetic Epilepsy and in the General Population. PLoS One 11:e0162883
Botzolakis, Emmanuel J; Gurba, Katharine N; Lagrange, Andre H et al. (2016) Comparison of ?-Aminobutyric Acid, Type A (GABAA), Receptor ??? and ??? Expression Using Flow Cytometry and Electrophysiology: EVIDENCE FOR ALTERNATIVE SUBUNIT STOICHIOMETRIES AND ARRANGEMENTS. J Biol Chem 291:20440-61
Janve, Vaishali S; Hernandez, Ciria C; Verdier, Kelienne M et al. (2016) Epileptic encephalopathy de novo GABRB mutations impair ?-aminobutyric acid type A receptor function. Ann Neurol 79:806-825
Kang, Jing-Qiong; Shen, Wangzhen; Zhou, Chengwen et al. (2015) The human epilepsy mutation GABRG2(Q390X) causes chronic subunit accumulation and neurodegeneration. Nat Neurosci 18:988-96

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