Effect of protein kinase-C activation on the Mg 2+-sensitivity of cloned NMDA receptors

Abstract

The mechanisms responsible for protein kinase-c (PKC) mediated potentiation of NMDA receptors are poorly understood. One hypothesis is that PKC-activation reduces the receptor's characteristic voltage-dependent Mg 2+-blockade. Experiments performed on Xenopus oocytes expressing cloned NMDA receptors demonstrated that PKC-activation induced no change in the sensitivity of ζl ε3 and ζ1 ε4 receptors to Mg 2+-blockade and, even though PKC-activation did induce a small shift in Mg 2+sensitivity for the ζl εl and ζl ε2 receptors, the change seen was not large enough to account for an appreciable increase in NMDA receptor activity. Baseline Mg 2+-sensitivities and levels of PKC-mediated potentiation were also quantified for each of the di-heteromeric NMDA receptors. The order of Mg 2+-sensitivity is ζl ε l (most sensitive) > ζl ε2 > | solζl g34 > l ε3 (least sensitive). PKC-activation caused a 2-fold increase in ζl g4 l currents, a 4-fold increase in 1 ε2 currents and no change in either l ε3 or l ε4 currents. These data suggest that PKC-potentiation of the cloned di-heteromeric NMDA receptors does not involve a reduction in Mg 2+-blockade. The di-heteromeric receptors possess varied properties in regard to PKC-potentiation and Mg 2+-blockade which have been quantified here.