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J Neurochem. 2008 Jul;106(1):182-92. doi: 10.1111/j.1471-4159.2008.05356.x. Epub 2008 Jul 1.

Regulation of Kv4.2 channels by glutamate in cultured hippocampal neurons.

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1
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

Abstract

Somatodendritic voltage-dependent K(+) currents (Kv4.2) channels mediate transient A-type K(+) currents and play critical roles in controlling neuronal excitability. Accumulating evidence has indicated that Kv4.2 channels are key regulatory components of the signaling pathways that lead to synaptic plasticity. In contrast to the extensive studies of glutamate-induced AMPA [(+/-) alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate] receptors redistribution, less is known about the regulation of Kv4.2 by glutamate. In this study, we report that brief treatment with glutamate rapidly reduced total Kv4.2 levels in cultured hippocampal neurons. The glutamate effect was mimicked by NMDA, but not by AMPA. The effect of glutamate on Kv4.2 was dramatically attenuated by pre-treatment of NMDA receptors antagonist MK-801 [(5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate] or removal of extracellular Ca(2+). Immunocytochemical analysis showed a loss of Kv4.2 clusters on the neuronal soma and dendrites following glutamate treatment, which was also dependent on the activation of NMDA receptors and the influx of Ca(2+). Furthermore, whole-cell patch-clamp recordings revealed that glutamate caused a hyperpolarized shift in the inactivation curve of A-type K(+) currents, while the activation curve remained unchanged. These results demonstrate a glutamate-induced alteration of Kv4.2 channels in cultured hippocampal neurons, which might be involved in activity-dependent changes of neuronal excitability and synaptic plasticity.

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