Excitatory action of N-acetylaspartylglutamate on Purkinje cells in guinea pig cerebellar slices: an intrasomatic study

Abstract

The action of N-acetylaspartylglutamate (NAAG) on Purkinje cell somata in guinea pig cerebellar slices was intracellularly investigated in comparison with l-aspartate (Asp) and l-glutamate (Glu). A synthetic NAAG sample used was confirmed not to be contaminated with free Glu and Asp. NAAG, applied by either iontophoresis or superfusion, dose-dependently depolarized Purkinje cell somata, and iontopheretically applied NAAG decreased the membrane resistance in voltage- and Mg 2+-dependent manners, like Asp or Glu. Relative depolarizing potencies seemed to be Glu>NAAG≑Asp in the presence of external Mg 2+ and Asp>NAAG⩽Glu in the absence of Mg 2+. In addition to this selective blocking effect of Mg 2+, 2-amino-5-phosphonovalerate (APV) antagonized the actions of NAAG and Asp more strongly than that of Glu, while 2-amino-4-phosphonobutyrate showed rather non-selective antagonisms. The reversal potential of the NAAG action was at about 10 mV and similar to that of the action of Asp or Glu. These results suggest that NAAG itself is excitatory to guinea pig cerebellar Purkinje cells and is likely to be acting on Asp- and APV-sensitive, Mg 2+-dependent receptors on cerebellar Purkinje cells.