Kainate-induced currents in rat cortical neurons in culture are modulated by riluzole
| Autor: | Silvio Cavalcanti, Giovanbattista De Sarro, Antonio Siniscalchi, Nicola Costa, Giorgio Bernardi, Nicola Biagio Mercuri, Caterina Marchetti, Chiara Gaetti, Cristina Zona |
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| Rok vydání: | 2002 |
| Předmět: |
Kainic acid
Neurotoxins Kainate receptor Neurotransmission Pharmacology Settore BIO/09 Ion Channels Cellular and Molecular Neuroscience chemistry.chemical_compound Fetus Receptors Kainic Acid Excitatory Amino Acid Agonists medicine Animals Receptors AMPA Patch clamp Rats Wistar Reversal potential Cells Cultured Cerebral Cortex Neurons Membrane potential Epilepsy Kainic Acid Riluzole Chemistry Amyotrophic Lateral Sclerosis Rats Neuroprotective Agents CNQX medicine.drug |
| Zdroj: | Synapse. 43:244-251 |
| ISSN: | 1098-2396 0887-4476 |
| Popis: | The action of the neuroprotective and anticonvulsant agent riluzole on kainate-induced currents was studied in rat cortical neurons in primary culture by using the whole-cell configuration of the patch-clamp technique. Kainate elicited macroscopic, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive inward currents in all the patched cells and the amplitude of the current was concentration-dependent (EC50= 106 μM). Riluzole decreased the inward currents induced by 100 μM kainate at all holding potentials and the reduction was dose-dependent (IC50= 101 μM). The maximal response to kainate decreased in the presence of 50 μM riluzole, without changing its EC50, indicating a noncompetitive mechanism of inhibition. The amplitude of the responses induced by kainate under control conditions and during riluzole was a linear function of the membrane potential and the reversal potential of the currents was not significantly different in the two experimental conditions. Instead, the total conductance of the cell membrane for the currents induced by 100 μM kainate was significantly reduced in the presence of 50 μM riluzole (P < 0.05). The analysis of the kainate membrane current noise performed under control conditions and during perfusion of 100 μM riluzole revealed that riluzole reduced the probability of kainate-activated ionic channels to be in the open state. Conversely, the unitary conductance of channels, as well as their characteristic time constant, seemed to be unchanged. These results reveal an additional mechanism by which riluzole can interact with glutamatergic neurotransmission and provides further support for the idea that riluzole may prove beneficial in the treatment of central nervous system injuries involving the excitotoxic actions of glutamate. Synapse 43:244–251, 2002. © 2002 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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