Effects of excitatory amino acids on cerebellar Purkinje cells in vitro: intradendritic study.

Abstract

Whether an excitatory neurotransmitter at climbing fiber(CF) synapses on Purkinje cell dendrites is L-glutamate(glu) or L-aspartate(asp) was electrophysiologically and pharmacologically investigated using intradendritic recordings from Purkinje cells in guinea pig cerebellar slices. Both glu and asp similarly depolarized Purkinje cell dendrites and decreased the membrane resistance by primarily increasing Na conductance. The reversal potential for glu and asp were about 7mV and 5mV, respectively, while the CF response was inverted at a membrane potential of about 1OmV and was also dependent on external Na concentrations. Physiologically, it was thus difficult to specify glu or asp to be a transmitter of the CF synapse. Pharmacologically, it was found that glutamic acid diethyl ester(GDEE) blocked the glu action7but not the action of asp, while N-methyl-D, L-aspartate(NMDLA) strongly depressed the asp action, but only mildly the glu action. DL-Aspartic acid dimethyl ester(ADME) strongly antagonized the asp action, while it potentiated the action of glu. The CF response was partially blocked by NMDLA, potentiated by ADME and markedly depressed by GDEE. These pharmacological findings suggest a possibility that glu, rather than asp, is a more likely excitatory neurotransmitter in climbing fibers, at least, in the guinea pig cerebellum.