Regional differences in nerve terminal Na+ channel subtype expression and Na+ channel-dependent glutamate and GABA release in rat CNS.
Regional differences in nerve terminal Na+ channel subtype expression and Na+ channel-dependent glutamate and GABA release in rat CNS.
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DOI：
10.1111/j.1471-4159.2010.06722.x
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发表时间：
2010-06
影响因子：
4.7
通讯作者：
Hemmings HC Jr
中科院分区：
文献类型：
--
作者：
Westphalen RI;Yu J;Krivitski M;Jih TY;Hemmings HC Jr
我们测试的假设，突触前电压门控Na+通道（Nav）亚型的表达耦合到神经递质的释放不同的递质类型和中枢神经系统区域之间的神经末梢特异性的方式。通过测量4-氨基吡啶（4-aminopyridine，4AP）诱发的[~ 3 H]谷氨酸和[~（14）C]GABA释放对从大鼠大脑皮层、海马、纹状体和脊髓分离的神经末梢的特异性Nav阻断剂河豚毒素（Tetrodotoxin，TTX）的敏感性来确定Nav与递质释放的耦合。使用亚型特异性抗体通过免疫印迹测量各种Nav亚型的表达。TTX抑制谷氨酸和GABA释放的潜力在CNS区域之间相似。然而，TTX抑制4AP诱发的谷氨酸释放的效力大于抑制GABA释放在除脊髓以外的所有区域。总Nav亚型以及特定亚型的相对神经末梢表达在CNS区域之间变化很大。TTX抑制4AP诱发的谷氨酸释放的区域特异性效力与总神经末梢Nav和Nav1.2的更大相对表达相关。特定Nav亚型表达的神经末梢特异性差异导致递质释放的药理学敏感性的递质特异性和区域差异。
We tested the hypothesis that expression of presynaptic voltage-gated Na+ channel (Nav) subtypes coupled to neurotransmitter release differs between transmitter types and CNS regions in a nerve terminal-specific manner. Nav coupling to transmitter release was determined by measuring the sensitivity of 4-aminopyridine (4AP)-evoked [3H]glutamate and [14C]GABA release to the specific Nav blocker tetrodotoxin (TTX) for nerve terminals isolated from rat cerebral cortex, hippocampus, striatum and spinal cord. Expression of various Nav subtypes was measured by immunoblotting using subtype-specific antibodies. Potencies of TTX for inhibition of glutamate and GABA release were similar between CNS regions. However, the efficacies of TTX for inhibition of 4AP-evoked glutamate release were greater than for inhibition of GABA release in all regions except spinal cord. The relative nerve terminal expression of total Nav subtypes as well as of specific subtypes varied considerably between CNS regions. The region-specific potencies of TTX for inhibition of 4AP-evoked glutamate release correlated with greater relative expression of total nerve terminal Nav and Nav1.2. Nerve terminal-specific differences in the expression of specific Nav subtypes contribute to transmitter-specific and regional differences in pharmacological sensitivities of transmitter release.
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影响因子：
3.5
作者：
Hemmings, HC
通讯作者：
Hemmings, HC
影响因子：
3.3
作者：
Mechaly, I;Scamps, F;Valmier, J
通讯作者：
Valmier, J
DOI：
10.1016/s0169-328x(96)00241-0
发表时间：
1997-04-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Felts, PA;Yokoyama, S;Waxman, SG
通讯作者：
Waxman, SG
影响因子：
2.9
作者：
DODD, PR;HARDY, JA;DELAUNOY, JP
通讯作者：
DELAUNOY, JP
影响因子：
4.7
作者：
HEMMINGS, HC;GIRAULT, JA;GREENGARD, P
通讯作者：
GREENGARD, P