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Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke
Published on: February 4, 2014
L-Phosphinothricin modulation of inwardly rectifying K(+) channels increased excitability in striatal medium-sized
Laetitia Domingos1, Agnès Desrus1, Sandra Même1
1Centre de Biophysique Moléculaire, CNRS UPR4301, Complexes métalliques et IRM pour applications biomédicales, Rue Charles Sadron, CS 80054, 45071, Orléans Cedex 2, France.
Abstract:
Phosphinotricin (L-PPT) is the active compound of a broad-spectrum herbicide. Acute poisoning with L-PPT has various clinical manifestations, including seizures and convulsions. However, the exact mechanism of L-PPT toxicity remains unclear. The present study addressed the role of L-PPT, in the excitability of striatal medium-sized spiny neurons (MSNs). In whole-cell current-clamp experiments, L-PPT increased the input resistance (Ri), decreased the rheobase and increased the firing frequency of action potentials. In voltage-clamp experiments, L-PPT inhibited the inward-rectifying potassium (Kir) currents. Finally, the effects of L-PPT mimicked the inhibition of Kir channels with Ba(2+) on neuronal excitability. Altogether, these results suggest that the herbicide L-PPT is a modulator of Kir channels in MSNs. Thereby, Kir channels are potent regulators of the excitability of MSNs and reduced open probability of these channels would generate a powerful upregulation of neuronal output. This effect may represent a possible mechanism for L-PPT dependent neuronal toxicity.
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