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Publication Type : Journal Article
Thematic Areas : Learning-Technologies, Medical Sciences, Biotech
Publisher : Neuron.
Source : Neuron, Volume 55, Issue 3, 2 August 2007, Pages 449-463.
Campus : Amritapuri
School : School of Biotechnology
Center : Amrita Mind Brain Center, Biotechnology, Computational Neuroscience and Neurophysiology
Department : biotechnology, Biotechnology Virtual Labs
Year : 2007
Abstract : Neurons integrate and encode complex synaptic inputs into action potential outputs through a process termed “intrinsic excitability.” Here, we report the essential contribution of fibroblast growth factor homologous factors (FHFs), a family of voltage-gated sodium channel binding proteins, to this process. Fhf1−/−Fhf4−/− mice suffer from severe ataxia and other neurological deficits. In mouse cerebellar slice recordings, WT granule neurons can be induced to fire action potentials repetitively (∼60 Hz), whereas Fhf1−/−Fhf4−/− neurons often fire only once and at an elevated voltage spike threshold. Sodium channels in Fhf1−/−Fhf4−/− granule neurons inactivate at more negative membrane potential, inactivate more rapidly, and are slower to recover from the inactivated state. Altered sodium channel physiology is sufficient to explain excitation deficits, as tested in a granule cell computer model. These findings offer a physiological mechanism underlying human spinocerebellar ataxia induced by Fhf4 mutation and suggest a broad role for FHFs in the control of excitability throughout the CNS.
Cite this Research Publication : Mitchell Goldfarb, Jon Schoorlemmer, Anthony Williams, Shyam Diwakar, Xiao Huang, Joanna Giza, Dafna Tchetchik, Kevin Kelley, Ana Vega, Gary Matthews, Paola Rossi, David Ornitz, and Egidio D’Angelo, “Fibroblast growth factor homologous factors control neuronal excitability through modulation of voltage-gated sodium channels”, Neuron, Volume 55, Issue 3, 2 August 2007, Pages 449-463.