Thyroid hormone regulates excitability in central neurons from postnatal rats.
A lack of thyroid hormone in the postnatal period causes an irreversible mental retardation, characterized by a slowing of thoughts and movements accompanied by prolonged latencies of several evoked potentials and slowed electroencephalographic rhythms. Here we show that in cultured hippocampal and cortical neurons from postnatal rats treatment with thyroid hormone not only up-regulates Na(+)-current densities but also increases rates of rise, amplitudes and firing frequencies of action potentials. Furthermore, we show that the regulation of the Na(+)-current density by thyroid hormones also occurs in vivo: recordings from acutely isolated cortical neurons obtained from hypothyroid, euthyroid and hyperthyroid postnatal rats showed that hypothyroidism decreases the ratio of Na(+) inward- to K(+) outward-currents while hyperthyroidism upregulates Na(+)-currents with respect to K(+)-currents. Our observation of a regulation of neuronal excitability by thyroid hormone offers a direct explanation for the origin of various neurological symptoms related to thyroid dysfunction.
Hoffmann
G
G
Department of Molecular Neurobiochemistry, Ruhr-University Bochum, NC7-170, Universitätsstrasse 150, D-44780 Bochum, Germany.
Dietzel
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ID
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology*; D006980:Hyperthyroidism / Q000503:physiopathology; D007037:Hypothyroidism / Q000503:physiopathology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects; D013963:Thyroid Hormones / Q000494:pharmacology / Q000502:physiology*
D015221:Potassium Channels; D015222:Sodium Channels; D013963:Thyroid Hormones; D012964:Sodium; D002118:Calcium