当前位置： SCI文献检索 > JOURNAL OF NEUROPHYSIOLOGY期刊下所有文献 > Actions of U-92032, a T-type Ca2+ channel antagonist, support a functional linkage between I(T) and slow intrathalamic rhythms.

Actions of U-92032, a T-type Ca2+ channel antagonist, support a functional linkage between I(T) and slow intrathalamic rhythms.

Abstract：

:Thalamic relay neurons express high levels of T-type Ca(2+) channels, which support the generation of robust burst discharges. This intrinsically mediated form of phasic spike firing is thought to be critical in the generation of slow (3-4 Hz) synchronous oscillatory activity of absence epilepsy. Recordings made from brain slices or whole animals have shown that slow synchronous absence-like activity can be abolished when Ca(2+)-dependent burst firing in relay neurons is interrupted by the pharmacological or genetic inactivation of T-channels. Because succinimide drugs act as incomplete and nonspecific antagonists, we tested whether the novel T-channel antagonist U-92032 could provide stronger support for a role of T-channels in slow oscillatory activity. Ca(2+)-dependent rebound (LTS) bursts were recorded using whole cell current clamp in relay cells of the ventral basal complex (VB) from thalamic slices of adult rats. We used LTS kinetics to measure the availability of T-channels in VB cells after TTX. U-92032 (1 and 10 microM) reduced the maximum rate of depolarization of the isolated LTS by 51% and 90%, respectively, compared with the 35% reduction due to 2 mM methylphenylsuccinimide (MPS), the active metabolite of the antiabsence drug methsuximide. U-92032 (1 and 10 microM) also suppressed evoked, slow oscillations in thalamic slices with a time course similar for observed intracellular effects. Unlike MPS, we observed no substantial effects of short-term U-92032 applications (< or =2 h) on the generation of action potentials in VB cells. Our findings show U-92032 is a more potent, effective, and specific T-channel antagonist than previously studied succinimide antiabsence drugs and that it dramatically reduces epileptiform synchronous activity. This suggests that U-92032 or other specific T-channel antagonists may provide effective drug treatments for absence epilepsy.

journal_name

J Neurophysiol

journal_title

Journal of neurophysiology

authors

Porcello DM,Smith SD,Huguenard JR

doi

10.1152/jn.00667.2002

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

177-85

issue

eissn

0022-3077

issn

1522-1598

journal_volume

pub_type

杂志文章

在线工具

Actions of U-92032, a T-type Ca2+ channel antagonist, support a functional linkage between I(T) and slow intrathalamic rhythms.