Intrinsic excitability is altered by hypothyroidism in the developing hippocampal CA1 pyramidal cells

Thyroid hormone plays an essential role in brain development, so its deficiency during a critical developmental period has been associated with profound neurological deficits, including irreversible mental retardation. Despite the importance of the disorder, the cellular mechanisms underlying these deficits remain largely unexplored. The aim of this study was to examine the effects of the absence of thyroid hormone on the postnatal development of membrane excitability of CA1 hippocampal pyramidal cells. Current clamp recordings in the whole cell patch clamp configuration showed that the action potential of cells from hypothyroid animals presented shorter width, slower depolarization, and faster repolarization rates compared with controls both in early postnatal and pre-weanling ages. Additionally, thyroid hormone deficiency reduced the intrinsic membrane excitability as measured by the reduced number of evoked action potentials for a given depolarizing slope and by the more depolarized firing threshold observed in hypothyroid animals. Then we analyzed the fast-repolarizing A- and D-type potassium currents, as they constitute one of the major factors underlying intrinsic membrane excitability. Hypothyroid rats showed increased A-current density and a reduced isolated ID-like current, accompanied by parallel changes in the expression of the channels responsible for these currents in the CA1 region: Kv4.2, Kv4.3, and Kv1.2. Therefore, we suggest that the increased A-current density, subsequent to an increment in its channel expression, together with the decrease of Na+-currents, might help explain the functional alterations in the neuronal discharge, in the firing threshold, and in the action potential repolarization of hypothyroid pyramidal neurons.

▶Congenital absence of thyroid hormone reduces the intrinsic membrane excitability. ▶Congenital hypothyroidism increases input resistance and reduces membrane capacitance. ▶Depolarization rates are decreased, repolarization rates are increased, and action potential rates are decreased in hypothyroid animals. ▶D-current density and the expression of its channels are depressed in hypothyroid animals. ▶A-current density and the expression of its channels are increased in hypothyroid animals.