title: Akinesia and freezing caused by Na+leak-current channel (NALCN) deficiency corrected by pharmacological inhibition of K+channels and gap junctions.
abstract: The Na+leak-current channel (NALCN) regulates locomotion, respiration, and intellectual development. Previous work highlighted striking similarities between characteristic movement phenotypes of NALCN-deficient animals (Drosophila and Caenorhabditis elegans) and the major symptoms of Parkinson's disease and primary progressive freezing gait. We have discovered novel physiological connections between the NALCN, K+channels, and gap junctions that mediate regulation of locomotion in C. elegans. Drugs that block K+channels and gap junctions or that activate Ca++channels significantly improve movement of NALCN-deficient animals. Loss-of-function of the NALCN creates an imbalance in ions, including K+and Ca++, that interferes with normal cycles of depolarization-repolarization. This work suggests new therapeutic strategies for certain human movement disorders. J. Comp. Neurol. 525:1109-1121, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center-Shreveport, Shreveport, Louisiana, USA.
authors.forename: Merve
authors.initials: M
authors.lastname: Kasap
authors.affiliation: Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center-Shreveport, Shreveport, Louisiana, USA.
authors.forename: Kendra
authors.initials: K
authors.lastname: Bonnett
authors.affiliation: Department of Biochemistry and Molecular Biology, LSU Health Sciences Center-Shreveport, Shreveport, Louisiana, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Aamodt
authors.affiliation: Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center-Shreveport, Shreveport, Louisiana, USA.|Department of Psychiatry, LSU Health Sciences Center-Shreveport, Shreveport, Louisiana, USA.
authors.forename: Donard S
authors.identifier: http://orcid.org/0000-0002-4201-0958
authors.initials: DS
authors.lastname: Dwyer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D004195:Disease Models, Animal; D020233:Gait Disorders, Neurologic / Q000378:metabolism / Q000503:physiopathology*; D017629:Gap Junctions / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism*; D015222:Sodium Channels / Q000172:deficiency*
chemical_list: D029742:Caenorhabditis elegans Proteins; C000619736:NALCN protein, C elegans; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels
keywords: C. elegans strains CB1068 (RRID: WB_CB1068) and CB1272 (RRID: WB_CB1272); K+ channels; NALCN; Parkinson's disease; freezing gait; gap junctions