Literature DB >> 21044638

Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons.

Bruno A Benítez1, Helen M Belálcazar, Agustín Anastasía, Daniel T Mamah, Charles F Zorumski, Daniel H Mascó, Daniel G Herrera, Gabriel A de Erausquin.   

Abstract

In primary cultures of mesencephalon small-conductance calcium-activated potassium channels (SK) are expressed in dopaminergic neurons. We characterized SK-mediated currents (I(SK)) in this system and evaluated their role on homeostasis against excitotoxicity. I(SK) amplitude was reduced by the glutamatergic agonist AMPA through a reduction in SK channel number in the membrane. Blockade of I(SK) for 12 h with apamin or NS8593 reduced the number of dopaminergic neurons in a concentration-dependent manner. The effect of apamin was not additive to AMPA toxicity. On the other hand, two I(SK) agonists, 1-EBIO and CyPPA, caused a significant reduction of spontaneous loss of dopaminergic neurons. 1-EBIO reversed the effects of both AMPA and apamin as well. Thus, I(SK) influences survival and differentiation of dopaminergic neurons in vitro, and is part of protective homeostatic responses, participating in a rapidly acting negative feedback loop coupling calcium levels, neuron excitability and cellular defenses. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
Copyright © 2010 Elsevier Ltd. All rights reserved.

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Year:  2010        PMID: 21044638      PMCID: PMC4301957          DOI: 10.1016/j.neuropharm.2010.10.024

Source DB:  PubMed          Journal:  Neuropharmacology        ISSN: 0028-3908            Impact factor:   5.250


  83 in total

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  11 in total

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9.  Subcellular expression and neuroprotective effects of SK channels in human dopaminergic neurons.

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