CORRELATION BETWEEN KINETICS AND RNA SPLICING OF LPHA-AMINO-3-HYDROXY-5-METHYLISOXAZOLE-4-PROPIONIC ACID RECEPTORS IN NEOCORTICAL NEURONS

In the cortex fast excitatory synaptic currents onto excitatory pyrami dal neurons and inhibitory nonpyramidal neurons are mediated by lpha-a mino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors exh ibiting cell-type-specific differences in their kinetic properties. AM PA receptors consist of four subunits (GluR1-4), each existing as two splice variants, flip and flop, which critically affect the desensitiz ation properties of receptors expressed in heterologous systems. Using single cell reverse transcription PCR to analyze the mRNA of AMPA rec eptor subunits expressed in layers I-III neocortical neurons, we find that 90% of the GluR1-4 in nonpyramidal neurons are flop variants, whe reas 92% of the GluR1-4 in pyramidal neurons are flip variants. We als o find that nonpyramidal neurons predominantly express GluR1 mRNA (Glu R1/GluR1-4 = 59%), whereas pyramidal neurons contain mainly GluR2 mRNA (GluR2/GluR1-4 = 59%). However, the neuron-type-specific splicing is exhibited by all four AMPA receptor subunits. We suggest that the pred ominance of the flop variants contributes to the faster and more exten sive desensitization in nonpyramidal neurons, compared to pyramidal ce lls where flip variants are dominant. Alternative splicing of AMPA rec eptors may play an important role in regulating synaptic function in a cell-type-specific manner, without changing permeation properties.