PT  - JOURNAL ARTICLE
AU  - Zhi-Gang Xiong
AU  - Ramin Raouf
AU  - Wei-Yang Lu
AU  - Lu-Yang Wang
AU  - Beverley A. Orser
AU  - Ellen M. Dudek
AU  - Michael D. Browning
AU  - John F. MacDonald
TI  - Regulation of <em>N</em>-Methyl-<span class="sc">d</span>-Aspartate Receptor Function by Constitutively Active Protein Kinase C
AID  - 10.1124/mol.54.6.1055
DP  - 1998 Dec 01
TA  - Molecular Pharmacology
PG  - 1055--1063
VI  - 54
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/54/6/1055.short
4100  - http://molpharm.aspetjournals.org/content/54/6/1055.full
SO  - Mol Pharmacol1998 Dec 01; 54
AB  - The ability of the constitutively active fragment of protein kinase C (PKM) to modulate N-methyl-d-aspartate (NMDA)-activated currents in cultured mouse hippocampal neurons and acutely isolated CA1 hippocampal neurons from postnatal rats was studied using patch-clamp techniques. The responses of two heterodimeric combinations of recombinant NMDA receptors (NR1a/NR2A and NR1a/NR2B) expressed in human embryonic kidney 293 cells were also examined. Intracellular applications of PKM potentiated NMDA-evoked currents in cultured and isolated CA1 hippocampal neurons. This potentiation was observed in the absence or presence of extracellular Ca2+ and was prevented by the coapplication of the inhibitory peptide protein kinase inhibitor(19–36). Furthermore, the PKM-induced potentiation was not a consequence of a reduction in the sensitivity of the currents to voltage-dependent blockade by extracellular Mg2+. We also found different sensitivities of the responses of recombinant NMDA receptors to the intracellular application of PKM. Some potentiation was observed with the NR1a/NR2A subunits, but none was observed with the NR1a/NR2B combination. Applications of PKM to inside-out patches taken from cultured neurons increased the probability of channel opening without changing single-channel current amplitudes or channel open times. Thus, the activation of protein kinase C is associated with potentiation of NMDA receptor function in hippocampal neurons largely through an increase in the probability of channel opening.