Multi-target novel neuroprotective compound ITH33/IQM9.21 inhibits calcium entry, calcium signals and exocytosis.

Abstract

Compound ITH33/IQM9.21 (ITH/IQM) belongs to a new family of l-glutamic acid derivatives with antioxidant and neuroprotective properties on in vitro and in vivo models of stroke. Because neuronal damage after brain ischemia is tightly linked to excess Ca2+ entry and neuronal Ca2+ overload, we have investigated whether compound ITH/IQM antagonises the elevations of the cytosolic Ca2+ concentrations ([Ca2+]c) and the ensuing exocytotic responses triggered by depolarisation of bovine chromaffin cells. In fluo-4-loaded cell populations, ITH/IQM reduced the K+-evoked [Ca2+]c transients with an IC50 of 5.31 μM. At 10 μM, the compound decreased the amplitude and area of the Ca2+ transient elicited by challenging single fura-2-loaded cells with high K+, by 40% and 80%, respectively. This concentration also caused a blockade of K+-induced catecholamine release at the single-cell level (78%) and cell populations (55%). These effects are likely due to blockade of the whole-cell inward Ca2+ currents (IC50=6.52 μM). At 10 μM, ITH/IQM also inhibited the Ca2+-dependent outward K+ current, leaving untouched the voltage-dependent component of IK. The inward Na+ current was unaffected. Inhibition of depolarisation-elicited Ca2+ entry, [Ca2+]c elevation and exocytosis could contribute to the neuroprotective effects of ITH/IQM in vulnerable neurons undergoing depolarisation during brain ischemia.

DOI: 10.1016/j.ceca.2011.06.006

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Cite this paper

@article{Maroto2011MultitargetNN, title={Multi-target novel neuroprotective compound ITH33/IQM9.21 inhibits calcium entry, calcium signals and exocytosis.}, author={Marcos Maroto and Antonio Miguel G de Diego and Elisa Albi{\~n}ana and Jos{\'e} Carlos Fern{\'a}ndez-Morales and Afonso Caricati-Neto and Aron Jurkiewicz and Matilde Y{\'a}{\~n}ez and Mar{\'i}a Isabel Rodr{\'i}guez-Franco and Santiago Javier Armesilla Conde and Mariana P Arce and Jes{\'u}s Miguel Hern{\'a}ndez-Guijo and Antonio G. Garc{\'i}a}, journal={Cell calcium}, year={2011}, volume={50 4}, pages={359-69} }