Formation of heteromeric gamma-aminobutyric acid type A receptors containing two different alpha subunits - PubMed (original) (raw)

Affiliations

PMID: 8145733

Formation of heteromeric gamma-aminobutyric acid type A receptors containing two different alpha subunits

T A Verdoorn. Mol Pharmacol. 1994 Mar.

Abstract

The functional properties of recombinant gamma-aminobutyric acid (GABA) receptors expressed transiently in human embryonic kidney 293 cells were examined. Combinations of alpha 1 beta 2 gamma 2, alpha 3 beta 2 gamma 2, and alpha 1 alpha 3 beta 2 gamma 2 subunits were transiently expressed and the properties of the resulting receptors were studied with patch-clamp electrophysiology. Each subunit combination produced receptors having a unique set of functional properties. Concentration-response experiments showed that receptors composed of alpha 1 beta 2 gamma 2 subunit combinations were more sensitive to GABA (EC50 = 17.4 microM) than were either alpha 3 beta 2 gamma 2 (EC50 = 103 microM) or alpha 1 alpha 3 beta 2 gamma 2 (EC50 = 55.8 microM) receptors. Consistent with its action at native GABA-A receptors, diazepam (1 microM) potentiated the effect of GABA by shifting the GABA concentration-response curve to the left. The magnitude of the diazepam shift also differed between subunit combinations. The apparent potency of GABA was increased 2-fold by diazepam with alpha 1 beta 2 gamma 2 receptors, 3-fold with alpha 3 beta 2 gamma 2 receptors, and 5-fold with alpha 1 alpha 3 beta 2 gamma 2 receptors. Brief applications (6-25 msec) of 3 mM GABA to outside-out patches revealed that currents decayed predominantly with double-exponential time courses. The decay time courses of currents mediated by alpha 1 beta 2 gamma 2 and alpha 1 alpha 3 beta 2 gamma 2 receptors were similar, whereas the alpha 3 beta 2 gamma 2 receptor response decayed more slowly. The distinct properties observed in cells expressing each of these subunit combinations suggest that the subunits form unique receptors. The possibility that some neuronal GABA receptors contain two different alpha subunits is discussed.

PubMed Disclaimer

Cited by

Expression of functional GABAA receptors in neuroendocrine gastropancreatic cells.
von Blankenfeld G, Turner J, Ahnert-Hilger G, John M, Enkvist MO, Stephenson F, Kettenmann H, Wiedenmann B. von Blankenfeld G, et al. Pflugers Arch. 1995 Jul;430(3):381-8. doi: 10.1007/BF00373913. Pflugers Arch. 1995. PMID: 7491262
New perspectives in the functional role of GABA(A) channel heterogeneity.
Vicini S. Vicini S. Mol Neurobiol. 1999 Apr;19(2):97-110. doi: 10.1007/BF02743656. Mol Neurobiol. 1999. PMID: 10371465 Review.
Kinetic differences between synaptic and extrasynaptic GABA(A) receptors in CA1 pyramidal cells.
Banks MI, Pearce RA. Banks MI, et al. J Neurosci. 2000 Feb 1;20(3):937-48. doi: 10.1523/JNEUROSCI.20-03-00937.2000. J Neurosci. 2000. PMID: 10648698 Free PMC article.
Altered cortical GABAA receptor composition, physiology, and endocytosis in a mouse model of a human genetic absence epilepsy syndrome.
Zhou C, Huang Z, Ding L, Deel ME, Arain FM, Murray CR, Patel RS, Flanagan CD, Gallagher MJ. Zhou C, et al. J Biol Chem. 2013 Jul 19;288(29):21458-21472. doi: 10.1074/jbc.M112.444372. Epub 2013 Jun 6. J Biol Chem. 2013. PMID: 23744069 Free PMC article.
Functional correlation of GABA(A) receptor alpha subunits expression with the properties of IPSCs in the developing thalamus.
Okada M, Onodera K, Van Renterghem C, Sieghart W, Takahashi T. Okada M, et al. J Neurosci. 2000 Mar 15;20(6):2202-8. doi: 10.1523/JNEUROSCI.20-06-02202.2000. J Neurosci. 2000. PMID: 10704495 Free PMC article.

Formation of heteromeric gamma-aminobutyric acid type A receptors containing two different alpha subunits - PubMed (original) (raw)