The role of GABAA receptors in the subsensitivity of Purkinje neurons to GABA in genetic epilepsy prone rats.
The GABA receptor subtype mediating responses of cerebellar Purkinje neurons to the neurotransmitter was evaluated and compared in GEPR-9 vs. nonepileptic, genetic control GEPR-NE rats. Quantitative analysis of responses to microiontophoretically applied GABA, muscimol and baclofen indicated that the inhibitory action of GABA on cerebellar Purkinje neurons was mediated by GABAA receptors since muscimol produced responses similar to those of GABA and baclofen was without substantial electrophysiological action. In addition, Purkinje neurons in GEPR-9 animals showed a similar reduced sensitivity to both GABA and muscimol. Radioligand binding studies using the GABAA receptor selective ligand, [3H]muscimol, and the benzodiazepine receptor selective ligand, [3H]flunitrazepam, were conducted on cerebellar and cortical homogenates from GEPR 9, GEPR-NE and Sprague-Dawley rats. No differences in the Kd or Bmax for these ligands among the three groups studied were observed. The lack of significant changes in the Kd and Bmax for these two ligands in the cerebellum suggests that the mechanism for the observed subsensitivity to GABA in the GEPR 9 rat lies beyond the level of the receptor, perhaps at the signal transduction process for GABA mediated inhibitory responses.
Gould
E M
EM
Department of Pharmacology and Toxicology, West Virginia University, Morgantown 26506-9223, USA.
Curto
K A
KA
Craig
C R
CR
Fleming
W W
WW
Taylor
D A
DA
D000818:Animals; D004198:Disease Susceptibility; D004827:Epilepsy / Q000235:genetics / Q000503:physiopathology*; D058785:GABA-A Receptor Agonists; D011689:Purkinje Cells / Q000187:drug effects*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid