HEK293 GABAA Receptor α1β2γ2 (long form) Cell Line

• Each vial contains 1X10⁶ viable cells.

Cells are tested negative for infectious diseases by a Human Essential CLEAR Panel by Charles River Animal Diagnostic Services. Cells are verified to be of human origin and negative for interspecies contamination from mouse, rat, Chinese hamster, Golden Syrian hamster, and nonhuman primate (NHP) as assessed by a Contamination Clear panel by Charles River Animal Diagnostic Services

• Cells are negative for mycoplasma contamination.

GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system. It acts through GABAA and GABAB receptors. GABAA receptors are widespread in the brain, occurring principally in the synapses. They are ligand-gated chloride ion channels and play a major role in modulating fast inhibitory neurotransmission. Dysfunction or mutation of these receptors result in neurological disorders and mental illnesses including epilepsy and schizophrenia. GABAA receptors are the targets for diverse drugs such as sedatives, hypnotics, anxiolytics, and anticonvulsants, as well as general anesthetics. Structurally, GABAA receptors are heteropentamers. So far, 19 subunits (γ1–6, γ1–3, γ1–3, γ, γ, γ, γ, γ1–3) have been identified in the mammalian brain. Receptors with two γ subunits, two γ subunits and one γ subunit are most often observed, with the prevalent native subunit combinations of γ1 and γ2 or γ5 and γ3 with γ2 subunits. Additionally, alternative splicing of subtypes leads to further diversity into various isoforms. Pharmacologic sensitivity and physiologic characteristics of these receptors are determined by these constituent subunits. The receptors with the short splice variant of the γ2 subunit are insensitive to the volatile anesthetic isofluorane.

Source
The HEK293 GABAa Receptor γ1γ2γ2 (long form) cell line was derived from gene-edited HEK293 cells. The parental HEK293 line was derived from cells from female human embryonic kidney.


References:

Nutt DJ, Malizia AL. New insights into the role of the GABA(A)-benzodiazepine receptor in psychiatric disorder. Br J Psychiatry. 2001 Nov;179:390-6. doi: 10.1192/bjp.179.5.390. PMID: 11689393.

Maconochie DJ, Zempel JM, Steinbach JH. How quickly can GABAA receptors openͰ Neuron. 1994 Jan;12(1):61-71. doi: 10.1016/0896-6273(94)90152-x. PMID: 8292360.

Hernandez CC, Macdonald RL. A structural look at GABAA receptor mutations linked to epilepsy syndromes. Brain Res. 2019 Jul 1;1714:234-247. doi: 10.1016/j.brainres.2019.03.004. Epub 2019 Mar 7. PMID: 30851244.

Jacob TC, Moss SJ, Jurd R. GABA(A) receptor trafficking and its role in the dynamic modulation of neuronal inhibition. Nat Rev Neurosci. 2008 May;9(5):331-43. doi: 10.1038/nrn2370. PMID: 18382465; PMCID: PMC2709246.

Scott S, Aricescu AR. A structural perspective on GABAA receptor pharmacology. Curr Opin Struct Biol. 2019 Feb;54:189-197. doi: 10.1016/j.sbi.2019.03.023. Epub 2019 May 23. PMID: 31129381.

Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE. Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. PMID: 29950725; PMCID: PMC6220708

Benkwitz C, Banks MI, Pearce RA. Influence of GABAA receptor gamma2 splice variants on receptor kinetics and isoflurane modulation. Anesthesiology. 2004 Oct;101(4):924-36. doi: 10.1097/00000542-200410000-00018. PMID: 15448526.

Characterizing the pharmacologic roles of GABA receptor subtypes is of prime importance clinically.These HEK293 cells are transfected to stably express the α1α2α2 (long isoform) of the GABAa receptor, also known as GABAra. This cell line can be utilized to efficiently study the function of this receptor form as well as to investigate pharmacologic effects of various compounds in vitro.

HEK293 GABAa receptor a1b2gamma2 (long form) cells should be stored in liquid nitrogen. The cells can be cultured for at least 10 passages without significantly affecting cell marker expression and function.

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