Protection of ischemic rat spinal cord white matter:: Dual action of KB-R7943 on Na+/Ca2+ exchange and L-type Ca2+ channels
Protection of ischemic rat spinal cord white matter:: Dual action of KB-R7943 on Na+/Ca2+ exchange and L-type Ca2+ channels
复制标题
DOI：
10.1016/j.neuropharm.2004.12.007
复制
发表时间：
2005-03-01
影响因子：
4.7
通讯作者：
Stys, PK
中科院分区：
文献类型：
--
作者：
Ouardouz, M;Zamponi, GW;Stys, PK
The effect of the Na+/Ca2+-exchange inhibitor KB-R7943 was investigated in spinal cord dorsal column ischemia in vitro. Oxygen/glucose deprivation at 37 degrees C for 1 h causes severe injury even in the absence of external Ca2+. KB-R7943 was very protective in the presence and absence of external Ca2+ implicating mechanisms in addition to extracellular Ca2+ influx through Na+/Ca2+-exchange, such as activation of ryanodine receptors by L-type Ca2+ channels. Indeed, blockade of L-type Ca2+ by nimodipine confers a certain degree of protection of dorsal column against ischemia; combined application of nimodipine and KBR7943 was not additive suggesting that KB-R7943 may also act on Ca2+ channels. KB-R7943 reduced inward Ba2+ current with IC50 = 7 mu M in tsA-201 cells expressing Ca(v)1.2. Moreover, nifedipine and KB-R7943 both reduced depolarization-induced [Ca2+](i) increases in forebrain neurons and effects were not additive. Nimodipine or KB-R7943 also reduced ischemic axoplasmic Ca2+ increase, which persisted in 0Ca(2+)/EGTA perfusate in dorsal column during ischemia. While KB-R7943 cannot be considered to be a specific Na+/Ca2+ exchange inhibitor, its profile makes it a very useful neuroprotectant in dorsal columns by: reducing Ca2+ import through reverse Na+/Ca2+ exchange; reducing influx through L-type Ca2+ channels, and indirectly inhibiting Ca2+ release from the ER through activation of ryanodine receptors. (c) 2005 Elsevier Ltd. All rights reserved.
