Differential expression of gamma-aminobutyric acid--a receptor subunits in rat dorsal and ventral hippocampus.
Recent data demonstrate weaker gamma-aminobutyric acid (GABA)-ergic inhibition in ventral (VH) compared with dorsal (DH) hippocampus. Therefore, we examined possible differences regarding the GABAA receptors between VH and DH as follows: 1) the expression of the GABAA receptor subunits (alpha1/2/4/5, beta1/2/3, gamma2, delta) mRNA and protein and 2) the quantitative distribution and kinetic parameters of [3H] muscimol (GABAA receptor agonist) binding. VH compared with DH showed: 1) lower levels for alpha1, beta2, gamma2 but higher levels for alpha2 and beta1 subunits in CA1, CA2, and CA3, the differences being more pronounced in CA1 region; in the CA1 region, the mRNA levels of alpha5 were higher, whereas those of alpha4 subunit were slightly lower; in dentate gyrus, the mRNA levels of alpha4, beta3, and delta subunits were significantly lower, presumably suggesting a lower expression of the alpha4/beta3/delta receptor subtype; and 2) lower levels of [3H]muscimol binding, with the lowest value observed in CA1, apparently resulting from weaker binding affinity, insofar as the KD values were higher in VH, whereas the Bmax values were similar between DH and VH. The differences in the subunit expression and the lower affinity of GABAA receptor binding observed predominantly in the CA1 region of VH suggest that the alpha1/beta2/gamma2 GABAA receptor subtype dominates in DH, and the alpha2/beta1/gamma2 subtype prevails in VH. This could underlie the lower GABAA-mediated inhibition observed in VH and, to some extent, explain 1) the higher liability of VH for epileptic activity and 2) the differential involvement of DH and VH in cognitive and emotional processes.
Sotiriou
Evangelos
E
Physiology Department, Medical School, University of Patras, Patras, Greece.
Papatheodoropoulos
Costas
C
Angelatou
Fevronia
F
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018755:GABA Agonists; C546240:GABRA1 protein, human; C484841:GABRA2 protein, human; C546242:Gabra1 protein, rat; C502185:Gabrb2 protein, rat; D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid