Involvement of the carboxyl-terminal region in modulation by tpa of the nmda receptor channel

The ∈l/ζl and ∈2/ζl heteromeric Af-methyl-D-aspartate (NMDA) receptor channels expressed in Xenopus oocytes, but not the ∈3/ζl and ∈4/ζl 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 sub-units between the ∈2 and ∈3 subunits. Functional analysis of heteromeric channels containing chimeric e subunits has shown that the carboxyl-terminal region of the e2 subunit is responsible for the activation of the ∈2/ζl channel by the TPA treatment.