SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release

被引:298
作者
Janz, R
Goda, Y
Geppert, M
Missler, M
Südhof, TC
机构
[1] Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Ctr Basic Neurosci, Dallas, TX 75235 USA
[2] Univ Texas, SW Med Ctr, Dept Mol Genet, Dallas, TX 75235 USA
[3] Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA
[4] Max Planck Inst Expt Med, Dept Mol Neurobiol, D-37075 Gottingen, Germany
关键词
D O I
10.1016/S0896-6273(00)81046-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
SV2 proteins are abundant synaptic vesicle proteins expressed in two major (SV2A and SV2B) and one minor isoform (SV2C) that resemble transporter proteins. We now show that SV2B knockout mice are phenotypically normal while SV2A- and SV2A/SV2B double knockout mice exhibit severe seizures and die postnatally. In electrophysiological recordings from cultured hippocampal neurons, SV2A- or SV2B-deficient cells exhibited no detectable abnormalities. Neurons lacking both SV2 isoforms, however, experienced sustained increases in Ca2+-dependent synaptic transmission when two or more action potentials were triggered in succession. These increases could be reversed by EGTA-AM. Our data suggest that without SV2 proteins, presynaptic Ca2+ accumulation during consecutive action potentials causes abnormal increases in neurotransmitter release that destabilize synaptic circuits and induce epilepsy.
引用
收藏
页码:1003 / 1016
页数:14
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