Up-Regulation of NR2B Subunit of NMDA Receptors in Cerebellar Granule Neurons by Ca2+/Calmodulin Kinase Inhibitor KN93
Article first published online: 13 NOV 2002
Journal of Neurochemistry
Volume 70, Issue 5, pages 1898–1906, May 1998
How to Cite
Corsi, L., Li, J. H., Krueger, K. E., Wang, Y. H., Wolfe, B. B. and Vicini, S. (1998), Up-Regulation of NR2B Subunit of NMDA Receptors in Cerebellar Granule Neurons by Ca2+/Calmodulin Kinase Inhibitor KN93. Journal of Neurochemistry, 70: 1898–1906. doi: 10.1046/j.1471-4159.1998.70051898.x
- Issue published online: 13 NOV 2002
- Article first published online: 13 NOV 2002
- Received November 7, 1997; revised manuscript received December 11, 1997; accepted December 12, 1997.
- Patch clamp;
- Glutamate receptors;
- Protein kinase;
- Granule cell development
Abstract: Recordings of NMDA-activated currents from cerebellar granule neurons in culture revealed a developmental increase in current density accompanied by a slight decrease of the half-maximal effective concentration. At the same time, a decrease of NMDA receptors comprising NR2B subunits was demonstrated by the reduction in the antagonism of NMDA currents by ifenprodil. Ifenprodil antagonism increased after treatment for 24 h with KN93- and KN62-selective inhibitors of the Ca2+/calmodulin-dependent protein kinases (CaM kinases), indicating a selective increase of receptor containing NR2B subunit. This increase was observed at all ages tested: 4 days in vitro (DIV4), DIV6, and DIV13. Western blot analysis with specific NMDA receptor antibodies performed at DIV6 confirmed the electrophysiological data. At this age, the negative control KN92 was ineffective. The increasing ifenprodil antagonism after KN93 treatment was proportionally greater in cells at DIV13 than at DIV4. Treatment with NMDA (100 µM) of cerebellar cultures for 24 h produced a decrease in the NMDA-induced current density by almost 50% at all ages tested. Ifenprodil antagonism, however, was unchanged. We propose that the expression of NR2B subunits in cerebellar granule cells is selectively stimulated by the inhibition of CaM kinases.