• J S Cruz, C Kushmerick, D C Moreira-Lobo, and F A Oliveira.
• Departamento de Bioquímica e Imunologia, Institudo de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901, Belo Horizonte - MG, Brazil.
• Neuroscience. 2012 Sep 27;221:108-14.

AbstractThiamine deficiency during embryonic or early postnatal development causes deficits in cerebellum-dependent activities including motor control and procedural memory. Here, we give a detailed description of the changes to A-type current in cultured cerebellar granule neurons exposed to thiamine deficiency in vitro. A-type current in treated neurons was reduced to 51% of that in controls. The remaining A-type current in treated neurons exhibited normal activation kinetics and voltage dependence whereas inactivation was markedly faster. These effects were selective because the delayed-rectifier potassium current density and kinetics were unchanged in thiamine-deficient neurons. A computational model of the cerebellar granule neuron was used to test the impact of these alterations and predicts an increase in excitability that is especially pronounced for synaptic activation. Our results suggest that the loss of A-type potassium conductance leads to hyperactivity in cerebellar granule neurons and may contribute to cell death observed in the granule layer of cerebellum during thiamine-deficiency in vivo.Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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