Up-regulation of dendritic Kv4.2 mRNA by activation of the NMDA receptor

Abstract

The localization of Kv4.2 mRNAs in dendritic regions suggests that Kv4.2 channels, which originate from on-site protein synthesis in the dendrites, might play a role in synaptic function. In this study, we determined the molecular mechanisms of dendritic transport of Kv4.2 mRNA. Three hours of incubation following a brief depolarization resulted in significant increases in Kv4.2 mRNA levels in both cell bodies and dendrites. The increase in the mRNA in the dendrites was mediated by transcription- and translation-independent mechanisms. In order to further clarify the molecular mechanism of dendritic transport of Kv4.2 mRNA, we used the GFP-MS2 reporting system. Consistent with the in situ data, depolarization resulted in significant increases in dendritic levels of Kv4.2 mRNA at the maximal length at which Kv4.2 mRNA could be detected. These increases were mediated in a synaptic NMDA receptor- and Ca(2+)-dependent fashion. Collectively, these results indicate that Kv4.2 mRNA levels are regulated in response to synaptic activity, and this phenomenon may be the mechanism underlying the homeostasis of Kv4.2 protein on dendritic surfaces.