Sánchez-Alonso, José LuisSánchez-Aguilera López, AlbertoVicente Torres, María ÁngelesColino Matilla, María Asunción2024-01-242024-01-242012J 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 5:207:37-510306-452210.1016/j.neuroscience.2012.01.030https://hdl.handle.net/20.500.14352/95150Thyroidhormoneplaysanessential 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Intrinsic excitability is altered by hypothyroidism in the developing hippocampal CA1 pyramidal cellsjournal article1873-754https://neurosciencenews.com/open access612.8A-typepotassiumcurrentD-typepotassiumcurrentKv4,Kv1.2NeuronaldischargeActionpotentialNeurociencias (Medicina)2490 Neurociencias