%0 Journal Article
%A Sánchez-Alonso, José Luis
%A Sánchez-Aguilera López, Alberto
%A Vicente Torres, María Ángeles
%A Colino Matilla, María Asunción
%T Intrinsic excitability is altered by hypothyroidism in the developing hippocampal CA1 pyramidal cells
%D 2012
%@ 0306-4522
%U https://hdl.handle.net/20.500.14352/95150
%X Thyroidhormoneplaysanessential roleinbrain development,soitsdeficiencyduringacriticaldevelopmentalperiodhasbeenassociatedwithprofoundneurological deficits,includingirreversiblementalretardation.Despitethe importanceof thedisorder, thecellularmechanismsunderlyingthesedeficitsremainlargelyunexplored.Theaimofthis studywastoexaminetheeffectsof theabsenceof thyroid hormoneonthepostnataldevelopmentofmembraneexcitabilityofCA1hippocampal pyramidal cells.Current clamp recordings in the whole cell patch clamp configuration showedthat theactionpotentialofcellsfromhypothyroid animalspresentedshorterwidth,slowerdepolarization,and faster repolarizationratescomparedwithcontrolsboth in earlypostnatalandpre-weanlingages.Additionally, thyroid hormonedeficiencyreducedthe intrinsicmembraneexcitabilityasmeasuredbythereducednumberofevokedaction potentials for agivendepolarizingslopeandby themore depolarizedfiring thresholdobserved inhypothyroidanimals.Thenweanalyzedthefast-repolarizingA-andD-type potassiumcurrents,astheyconstituteoneofthemajorfactorsunderlyingintrinsicmembraneexcitability.Hypothyroid ratsshowedincreasedA-currentdensityandareducedisolatedID-likecurrent,accompaniedbyparallelchangesinthe expressionofthechannelsresponsibleforthesecurrentsin theCA1region:Kv4.2,Kv4.3,andKv1.2.Therefore,wesuggest that theincreasedA-currentdensity,subsequent toan increment in itschannel expression, togetherwiththedecreaseof Na-currents,might helpexplain the functional alterationsintheneuronaldischarge, inthefiringthreshold, andintheactionpotential repolarizationofhypothyroidpyramidalneurons.©2012IBRO.PublishedbyElsevierLtd.All rightsreserved.
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