期刊
JOURNAL OF NEUROCHEMISTRY
卷 111, 期 3, 页码 745-756出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1471-4159.2009.06368.x
关键词
[Ca2+](i); [Na+](i); CA1 pyramidal cells; epilepsy; non-inactivating VGSCs; veratridine
资金
- Hungarian Medical Research Foundation [576/2006]
- Hungarian Research Found [OTKA TS 049868, OTKA NK 72959]
Although the role of Na+ in several aspects of Ca2+ regulation has already been shown, the exact mechanism of intracellular Ca2+ concentration ([Ca2+](i)) increase resulting from an enhancement in the persistent, non-inactivating Na+ current (I-Na,I-P), a decisive factor in certain forms of epilepsy, has yet to be resolved. Persistent Na+ current, evoked by veratridine, induced bursts of action potentials and sustained membrane depolarization with monophasic intracellular Na+ concentration ([Na+](i)) and biphasic [Ca2+](i) increase in CA1 pyramidal cells in acute hippocampal slices. The Ca2+ response was tetrodotoxin- and extracellular Ca2+-dependent and ionotropic glutamate receptor-independent. The first phase of [Ca2+](i) rise was the net result of Ca2+ influx through voltage-gated Ca2+ channels and mitochondrial Ca2+ sequestration. The robust second phase in addition involved reverse operation of the Na+-Ca2+ exchanger and mitochondrial Ca2+ release. We excluded contribution of the endoplasmic reticulum. These results demonstrate a complex interaction between persistent, non-inactivating Na+ current and [Ca2+](i) regulation in CA1 pyramidal cells. The described cellular mechanisms are most likely part of the pathomechanism of certain forms of epilepsy that are associated with I-Na,I-P. Describing the magnitude, temporal pattern and sources of Ca2+ increase induced by I-Na,I-P may provide novel targets for antiepileptic drug therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据