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Selective Blockade of N‐Type Calcium Channels by Levetiracetam
Author(s) -
Lukyanetz E. A.,
Shkryl V. M.,
Kostyuk P. G.
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2002.24501.x
Subject(s) - chemistry , voltage dependent calcium channel , hippocampal formation , patch clamp , inhibitory postsynaptic potential , biophysics , calcium channel , t type calcium channel , stimulation , l type calcium channel , p type calcium channel , calcium , neuroscience , biochemistry , biology , receptor , organic chemistry
Summary: Purpose: We investigated the effect of the new antiepileptic drug (AED) levetiracetam (LEV) on different types of high‐voltage–activated (HVA) Ca 2+ channels in freshly isolated CA1 hippocampal neurons of rats. Methods: Patch‐clamp recordings of HVA Ca 2+ channel activity were obtained from isolated hippocampal CA1 neurons. LEV was applied by gravity flow from a pipette placed near the cell, and solution changes were made by electromicrovalves. Ca 2+ channel blockers were used for separation of the channel subtypes. Results: The currents were measured in controls and after application of 1–200 μ M LEV. LEV irreversibly inhibited the HVA calcium current by ∼18% on the average. With a prepulse stimulation protocol, which can eliminate direct inhibition of Ca 2+ channels by G proteins, we found that G proteins were not involved in the pathways underlying the LEV inhibitory effect. This suggested that the inhibitory effect arises from a direct action of LEV on the channel molecule. The blocking mechanism of LEV was not related to changes in steady‐state activation or inactivation of Ca 2+ channels. LEV also did not influence the rundown of the HVA Ca 2+ current during experimental protocols lasting ∼10 min. Finally, LEV at the highest concentration used (200 μ M ) did not influence the activity of L‐, P‐ or Q‐type Ca 2+ channels in CA1 neurons, while selectively influencing the activity of N‐type calcium channels. The maximal effect on these channels separated from other channel types was ∼37%. Conclusions: Our results provide evidence that LEV selectively inhibits N‐type Ca 2+ channels of CA1 pyramidal hippocampal neurons. These data suggest the existence of a subtype of N‐type channels sensitive to LEV, which might be involved in the molecular basis of its antiepileptic action.