Regulation of N-methyl-D-aspartate receptor function by constitutively active protein kinase C.

Content Provider	Semantic Scholar
Author	Xiong, Z. G. Raouf, Ramin Lu, Wen Ying Wang, Li Ying Orser, Bev A. Dudek, Ellen M. Browning, Michael D. Donald, John F. Mac
Copyright Year	1998
Abstract	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.
Starting Page	834
Ending Page	837
Page Count	4
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://molpharm.aspetjournals.org/content/molpharm/54/6/1055.full.pdf
PubMed reference number	9855634v1
Volume Number	54
Issue Number	6
Journal	Molecular pharmacology
Language	English
Access Restriction	Open
Subject Keyword	Aspartic Acid CA1 field GRIN2A wt Allele Hippocampus (Brain) N-Methyl-D-Aspartate Receptors N-Methylaspartate PKM gene PKM2 wt Allele Patch-Clamp Techniques Protein Kinase C Protein Kinases Recombinants Renal Tissue Vitamin D3 Receptor chemosensitization/potentiation
Content Type	Text
Resource Type	Article