UP-REGULATION OF THE GABA(A) BENZODIAZEPINE RECEPTOR DURING ANOXIA IN THE FRESH-WATER TURTLE BRAIN

The freshwater turtle brain survives anoxia by decreasing its energy expenditure. During this anoxic period there is a sustained release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). This study investigated whether there was a corresponding change in the binding properties of the GABA(A)/benzodiazepine (GABA/BDZ) receptor. Turtles (Trachemys scripta) were subjected to a 100% N-2 atmosphere for up to 24 h. After exposure, the cerebral cortex was dissected out, and saturation binding assays for GABA/BDZ receptors were performed using the radioligand [H-3]flunitrazepam. Control turtles had a dissociation constant (K-d) of 1.97 +/- 0.54 nM and a receptor density (B-max) of 2,404 +/- 221 fmol/mg protein. The K-d showed no significant change over 24 h of anoxia. However, significant increases were seen in B-max after 12 h (21%, P < 0.05) and 24 h (29%, P < 0.01) of anoxia. We suggest that a long-term upregulation of GABA(A) receptors occurs in the anoxic turtle brain that acts to increase the inhibitory effectiveness of the released GABA and thereby contributes to anoxia survival of the turtle.