부산대학교 도서관

J. Neurochem. (2010) 114, 191–202. NMDA receptors (NMDAR) contribute to neuronal development throughout the CNS. However, their mode(s) of activation preceding synaptic maturation is unclear, as they are not co-localized with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) which normally provide sufficient depolarization to relieve voltage-dependent blockade by Mg2+. We used cerebellar granule neurons (CGNs) cultured at a near-physiological KCl concentration to examine maturation-dependent changes in NMDAR responses. In contrast, most studies use KCl-supplemented medium to promote survival. At 2–4 days in vitro CGNs: (i) express developmental markers resembling the in vivo migratory phenotype; (ii) maintain a basal amount of calcium responsive element-binding protein phosphorylation that requires NMDARs and calcium/calmodulin-dependent kinases, but not AMPARs; (iii) exhibit NMDA-mediated Ca2+ influx not effectively blocked by ambient Mg2+ (0.75 mM) or AMPARs; (iv) maintain a more depolarized resting membrane potential and increased resistance compared to synaptically-connected CGNs. Moreover, migrating CGNs in explant cultures demonstrate NMDA-mediated Ca2+ influx not effectively blocked by 0.75 mM Mg2+, and NMDAR but not AMPAR antagonists slow migration. These data suggest the biophysical properties of immature CGNs render NMDARs less sensitive to Mg2+ blockade, enhancing the likelihood of activation in the absence of AMPAR depolarization. [ABSTRACT FROM AUTHOR]