RT Journal Article
T1 Intrinsic excitability is altered by hypothyroidism in the developing hippocampal CA1 pyramidal cells
A1 Sánchez-Alonso, José Luis
A1 Sánchez-Aguilera López, Alberto
A1 Vicente Torres, María Ángeles
A1 Colino Matilla, María Asunción
AB 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.
PB ElSevier
SN 0306-4522
YR 2012
FD 2012
LK https://hdl.handle.net/20.500.14352/95150
UL https://hdl.handle.net/20.500.14352/95150
LA eng
NO J L Sánchez-Alonso, A Sánchez-Aguilera, M A Vicente-Torres, A Colino. Intrinsic excitability is altered by hypothyroidism in the developing hippocampal CA1 pyramidal cells. Neuroscience. 2012 Apr 5:207:37-51
DS Docta Complutense
RD 10 abr 2025