Possible involvement of Rap1 and Ras in glutamatergic synaptic transmission.

Abstract

Rap1A, first identified as a suppressor of transformed phenotype induced by an activated ras oncogene, is abundantly expressed in the brain. Its neurophysiological function, however, is poorly understood. When an activated Rap1A mutant (Rap1-12V) or a dominant negative H-Ras mutant (Ras-17N) was expressed in CA1 neurons in cultured hippocampal slices using the sindbis virus-mediated gene transfer technique, NMDA receptor current in response to Schaffer collateral stimulation was suppressed. Expression of activated H-Ras mutant (Ras-12V) resulted in the elevation of both NMDA receptor current and AMPA receptor current. These results implicate counteracting functions of Ras and Rap1 in the regulation of NMDA receptor-mediated synaptic transmission and a positive regulatory role of Ras in AMPA receptor-mediated synaptic transmission.