INVOLVEMENT OF THE CARBOXYL-TERMINAL REGION IN MODULATION BY TPA OF THE NMDA RECEPTOR CHANNEL

THE epsilon1/zeta1 and epsilon2/zeta1 heteromeric N-methyl-D-aspartate (NMDA) receptor channels expressed in Xenopus oocytes, but not the epsilon3/zeta1 and epsilon4/zeta1 channels, are positively modulated by the treatment with 12-O-tetradecanoyl phorbol 13-acetate (TPA). Failure of potentiation in the presence of staurosporine suggests the involvement of protein kinases in the TPA effect. To identify the structural domain involved in the modulation of the NMDA receptor channel by the TPA treatment, we constructed chimeric subunits between the epsilon2 and epsilon3 subunits. Functional analysis of heteromeric channels containing chimeric epsilon subunits has shown that the carboxyl-terminal region of the epsilon2 subunit is responsible for the activation of the epsilon2/zeta1 channel by the TPA treatment.