title: Potassium channel Kv2.1 is regulated through protein phosphatase-1 in response to increases in synaptic activity.
abstract: The functional stability of neurons in the face of large variations in both activity and efficacy of synaptic connections suggests that neurons possess intrinsic negative feedback mechanisms to balance and tune excitability. While NMDA receptors have been established to play an important role in glutamate receptor-dependent plasticity through protein dephosphorylation, the effects of synaptic activation on intrinsic excitability are less well characterized. We show that increases in synaptic activity result in dephosphorylation of the potassium channel subunit Kv2.1. This dephosphorylation is induced through NMDA receptors and is executed through protein phosphatase-1 (PP1), an enzyme previously established to play a key role in regulating ligand gated ion channels in synaptic plasticity. Dephosphorylation of Kv2.1 by PP1 in response to synaptic activity results in substantial shifts in the inactivation curve of IK, resulting in a reduction in intrinsic excitability, facilitating negative feedback to neuronal excitability.
authors.affiliation: Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA, United States. Electronic address: bsiddo@scripps.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Siddoway
authors.affiliation: Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA, United States.
authors.forename: Hailong
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Structural and Cellular Biology, School of Medicine, Tulane University, New Orleans, LA, United States.
authors.forename: Jinnan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA, United States.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA, United States.
authors.forename: Hongtian
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Structural and Cellular Biology, School of Medicine, Tulane University, New Orleans, LA, United States.
authors.forename: Guo-yong
authors.initials: GY
authors.lastname: Wang
authors.affiliation: Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA, United States.
authors.forename: Houhui
authors.initials: H
authors.lastname: Xia
mesh_terms: D000818:Animals; D025461:Feedback, Physiological; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D061251:Primary Cell Culture; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D051669:Shab Potassium Channels / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*
chemical_list: C496991:Kcnb1 protein, rat; D016194:Receptors, N-Methyl-D-Aspartate; D051669:Shab Potassium Channels; D054645:Protein Phosphatase 1
keywords: Dephosphorylation; Kv2.1; NMDA receptor; PP1; Synaptic activity