N-methyl-D-aspartate receptors mediate activity-dependent down-regulation of potassium channel genes during the expression of homeostatic intrinsic plasticity

Kwan Young Lee, Sara E. Royston, Max O. Vest, Daniel J. Ley, Seungbae Lee, Eric C. Bolton, Hee Jung Chung

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Homeostatic intrinsic plasticity encompasses the mechanisms by which neurons stabilize their excitability in response to prolonged and destabilizing changes in global activity. However, the milieu of molecular players responsible for these regulatory mechanisms is largely unknown. Results: Using whole-cell patch clamp recording and unbiased gene expression profiling in rat dissociated hippocampal neurons cultured at high density, we demonstrate here that chronic activity blockade induced by the sodium channel blocker tetrodotoxin leads to a homeostatic increase in action potential firing and down-regulation of potassium channel genes. In addition, chronic activity blockade reduces total potassium current, as well as protein expression and current of voltage-gated Kv1 and Kv7 potassium channels, which are critical regulators of action potential firing. Importantly, inhibition of N-Methyl-D-Aspartate receptors alone mimics the effects of tetrodotoxin, including the elevation in firing frequency and reduction of potassium channel gene expression and current driven by activity blockade, whereas inhibition of L-type voltage-gated calcium channels has no effect. Conclusions: Collectively, our data suggest that homeostatic intrinsic plasticity induced by chronic activity blockade is accomplished in part by decreased calcium influx through N-Methyl-D-Aspartate receptors and subsequent transcriptional down-regulation of potassium channel genes.

Original languageEnglish (US)
Article number4
JournalMolecular Brain
Volume8
Issue number1
DOIs
StatePublished - Dec 2015

Keywords

  • Action potential
  • Hippocampus
  • Homeostatic intrinsic plasticity
  • NMDA receptor
  • Potassium channel

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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