GABA_B‐receptor splice variants GB1a and GB1b in rat brain: developmental regulation, cellular distribution and extrasynaptic localization

Abstract

GABAB (gamma-aminobutyric acid)-receptors have been implicated in central nervous system (CNS) functions, e.g. cognition and pain perception, and dysfunctions including spasticity and absence epilepsy. To permit an analysis of the two known GABAB-receptor splice variants GABAB-R1a (GB1a) and GABAB-R1b (GB1b), their distribution pattern has been differentiated in the rat brain, using Western blotting and immunohistochemistry with isoform-specific antisera. During postnatal maturation, the expression of the two splice variants was differentially regulated with GB1a being preponderant at birth. In adult brain, GB1b-immunoreactivity (-IR) was predominant, and the two isoforms largely accounted for the pattern of GABAB-receptor binding sites in the brain. Receptor heterogeneity was pronounced in the hippocampus, where both isoforms occurred in CA1, but only GB1b in CA3. Similarly, in the cerebellum, GB1b was exclusively found in Purkinje cells in a zebrin-like pattern. The staining was most pronounced in Purkinje cell dendrites and spines. Using electron microscopy, over 80% of the spine profiles in which a synaptic contact with a parallel fibre was visible contained GB1b-IR at extrasynaptic sites. This subcellular localization is unrelated to GABAergic inputs, indicating that the role of GABAB-receptors in vivo extends beyond synaptic GABAergic neurotransmission and may, in the cerebellum, involve taurine as a ligand.

Role of γ-aminobutyric acid B (GABAB) receptors in the regulation of kainic acid-induced cell death in mouse hippocampus

“…Immunocytochemical studies have revealed that GABAB receptors are distributed throughout the striatum, hippocampus, DG, hypothalamus, tectum, cerebellum, brainstem and spinal cord of rat (Fritschy et al, 1999;Margeta-Mitrovic et al, 1999;Calver et al, 2000). In the present study, we found that i.c.v.…”

γ-Aminobutyric Acid Type B Receptors Are Constitutively Internalized via the Clathrin-dependent Pathway and Targeted to Lysosomes for Degradation

“…To gain the first insights into the mechanisms involved in endocytosis of GABA B receptors, we expressed in HEK 293 cells the GABA B1b /GABA B2 combination, which is the most abundant GABA B receptor subtype in the adult brain (10,11). Heterologous expression of receptors was chosen, since it is a robust, easy to manipulate and to evaluate system.…”

The GABA B receptor interacts directly with the related transcription factors CREB2 and ATFx

“…This signaling pathway may be important during development of the nervous system. GABA B receptors are highly regulated during development with changes occurring in the levels of the splice variants and subunits (38)(39)(40). Changes in the relative levels of GABA B -R1͞GABA B -R2 may alter the ability of the GABA B receptor to interact with transcription factors and thereby regulate changes in gene expression during development.…”