Levetiracetam does not modulate neuronal voltage-gated Na+ and T-type Ca2+ currents.
This study investigated whether the mechanism of action of levetiracetam (LEV) is related to effects on neuronal voltage-gated Na+ or T-type Ca2+currents. Rat neocortical neurones in culture were subjected to the whole-cell mode of voltage clamping under experimental conditions designed to study voltage-gated Na+ current. Additionally, visually identified pyramidal neurones in the CA1 area of rat hippocampal slices were subjected to the whole-cell mode of voltage clamping under experimental conditions designed to study low-voltage-gated (T-type) Ca2+ current. LEV (10 microM-1 mM) did not modify the Na+ current amplitude and did not change (200 microM) the steady-state activation and inactivation, the time to peak, the fast kinetics of the inactivation and the recovery from the steady-state inactivation of the Na+ current. Likewise, LEV (32-100 microM) did not modify the amplitude and did not change the steady-state activation and inactivation, the time to peak, the fast kinetics of the inactivation and the recovery from the steady-state inactivation of the T-type Ca2+current. In conclusion, neuronal voltage-gated Na+ channels do not appear directly involved in the antiepileptic mechanism of action of LEV, and LEV was devoid of effect on the low-voltage-gated (T-type) Ca2+ current in hippocampal neurones.
Zona
C
C
Department of Neuroscience, University of Rome Tor Vergata and IRCCS Fondazione S. Lucia, Via Ardeatina, Rome, 306, Italy.
Niespodziany
I
I
Marchetti
C
C
Klitgaard
H
H
Bernardi
G
G
Margineanu
D G
DG
D000818:Animals; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D000077287:Levetiracetam; D009474:Neurons / Q000187:drug effects*; D018697:Nootropic Agents / Q000494:pharmacology*; D010889:Piracetam / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar / Q000196:embryology; D015222:Sodium Channels / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects; D013788:Thalamus / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D020747:Calcium Channels, T-Type; D018697:Nootropic Agents; D015222:Sodium Channels; D000077287:Levetiracetam; D005680:gamma-Aminobutyric Acid; D010889:Piracetam