title: N-methyl-D-aspartate receptors mediate activity-dependent down-regulation of potassium channel genes during the expression of homeostatic intrinsic plasticity.
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.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. lky@life.illinois.edu.
authors.forename: Kwan Young
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Program in Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA. sroysto2@illinois.edu.|Medical Scholars Program, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA. sroysto2@illinois.edu.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Royston
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. vest2@illinois.edu.
authors.forename: Max O
authors.initials: MO
authors.lastname: Vest
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. ley.danielj@gmail.com.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ley
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. lee852@illinois.edu.
authors.forename: Seungbae
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. boltonec@life.illinois.edu.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Bolton
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, 524 Burrill Hall, Urbana, IL, 61801, USA. chunghj@life.illinois.edu.|Program in Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois, 61801, USA. chunghj@life.illinois.edu.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Chung
mesh_terms: D000200:Action Potentials; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics*; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006624:Hippocampus / Q000166:cytology; D006706:Homeostasis; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate