Effect of protein kinase-C activation on the Mg(2+)-sensitivity of cloned NMDA receptors.
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 zeta 1/epsilon 3 and zeta 1/epsilon 4 receptors to Mg(2+)-blockade and, even though PKC-activation did induce a small shift in Mg2+ sensitivity for the zeta 1/epsilon 1 and zeta 1/epsilon 2 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 zeta 1/epsilon 1 (most sensitive) > zeta 1/epsilon 2 > zeta 1/epsilon 4 > zeta 1/epsilon 3 (least sensitive). PKC-activation caused a 2-fold increase in zeta 1/epsilon 1 currents, a 4-fold increase in zeta 1/epsilon 2 currents and no change in either zeta 1/epsilon 3 or zeta 1/epsilon 4 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.
Wagner
D A
DA
Department of Biological Sciences, University of Illinois at Chicago, USA.
Leonard
J P
JP
D000818:Animals; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000502:physiology*; D008274:Magnesium / Q000502:physiology*; D009865:Oocytes; D011493:Protein Kinase C / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D014981:Xenopus
D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D011493:Protein Kinase C; D008274:Magnesium