Premium
Kainate‐induced currents in rat cortical neurons in culture are modulated by riluzole
Author(s) -
Zona Cristina,
Cavalcanti Silvio,
De Sarro Giovanbattista,
Siniscalchi Antonio,
Marchetti Caterina,
Gaetti Chiara,
Costa Nicola,
Mercuri Nicola,
Bernardi Giorgio
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10040
Subject(s) - riluzole , kainate receptor , chemistry , biophysics , neuroscience , glutamate receptor , pharmacology , cnqx , patch clamp , membrane potential , ampa receptor , glutamatergic , electrophysiology , biochemistry , receptor , medicine , biology
Abstract 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 (EC 50 = 106 μM). Riluzole decreased the inward currents induced by 100 μM kainate at all holding potentials and the reduction was dose‐dependent (IC 50 = 101 μM). The maximal response to kainate decreased in the presence of 50 μM riluzole, without changing its EC 50 , 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.