AGE-RELATED-CHANGES OF GABA-ACTIVATED CHLORIDE CHANNEL PROPERTIES IN BRAIN CORTEX SYNAPTIC PLASMA-MEMBRANE - EVIDENCE FOR PHOSPHOLIPASE INVOLVEMENT

Brain aging decreases binding of tert-butylbicyclophosphorothionate (T BPS), a specific ligand for Cl- channels, but has no effect on Cl- inf lux. Detailed studies on the kinetics of TBPS dissociation allowed the characterization of Cl- channel properties. Aging lowers, exclusively in the presence of GABA agonist, muscimol, the half-life of the fast phase of TBPS dissociation, indicating an opening time of receptor-dep endent Cl- channels shorter than that in adult brain. The half-life of the slow phase of TBPS dissociation is significantly lower in aged br ain in the presence and absence of muscimol. These results suggest a s ustained Cl- current, including also the other channel(s) not connecte d with GABA(A) receptor activation. The analysis of biphasic TBPS diss ociation demonstrates a lowered number of binding sites resulted in th e reduction of the number of Cl- channels in the ''open'' state. This may explain an observed decrease of TBPS binding in aged brain. One of the possible factors involved in modification of GABAA receptor behav ior during aging may be arachidonic acid or diacylglycerol, known to b e accumulated in aged brain. The action of these compounds on the Cl- channel, observed in this study, correlates well with the effect of ag ing.