Effects of riluzole on rat cortical neurones: an in vitro electrophysiological study.
1. The electrophysiological effects of riluzole on rat prefrontal and frontal cortical neurones were investigated by using both extracellular (field) and intracellular recording techniques in brain slices. 2. Bath applied riluzole (3-200 microM) depressed the cortico-cortical stimulus-evoked field potential in a concentration-related manner (EC50 = 29.5 microM). 3. Riluzole (3-100 microM) reduced the tonic firing of the neocortical neurones which was caused by intracellular current injection, while it did not have any effect on the resting membrane potential and apparent input resistance of these cells. 4. In the presence of tetrodotoxin (1 microM) and tetraethylammonium (30 mM), the injection of a depolarizing current step generated a calcium spike in the neocortical neurones. Riluzole (30 microM) abolished this calcium-dependent action potential. However, when the amount of the depolarizing current was increased the calcium-dependent regenerative potential was evoked again. 5. The depolarization of the membrane (10-20 mV) caused by brief (8-15 s) bath applications of glutamate (300 microM-1 mM) were not changed in the presence of riluzole (30 microM). 6. It is concluded that riluzole has direct actions on rat neocortical neurones: (a) it blocks the repetitive discharge of sodium action potentials and (b) it increases the threshold for the generation of the calcium spike. These two cellular mechanisms might at least in part account for the depression of the cortico-cortical field potential caused by this drug.
Siniscalchi
A
A
IRCCS, Clinica Santa Lucia, Roma, Italy.
Bonci
A
A
Mercuri
N B
NB
Bernardi
G
G
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole; D013844:Thiazoles / Q000494:pharmacology*
D018696:Neuroprotective Agents; D013844:Thiazoles; D018698:Glutamic Acid; D019782:Riluzole; D002118:Calcium