Activation of metabotropic GABA receptors increases the energy barrier for vesicle fusion
Activation of metabotropic GABA receptors increases the energy barrier for vesicle fusion
复制标题
代谢型 GABA 受体的激活增加了囊泡融合的能量屏障
作者：
Benjamin R. Rost;Patrick D. Nicholson;G. Ahnert;A. Rummel;Christian Rosenmund;J. Breustedt;D. Schmitz
突触前末梢的神经递质释放受多种代谢型受体的严格控制。我们在这里报告，除了钙离子通道活性的调节，代谢型GABAB受体（GABABRs）在小鼠海马神经元突触利用抑制途径，直接针对突触囊泡释放机械。GABABR激动剂巴氯芬的急性应用快速且可逆地抑制囊泡融合，其独立于SNAP-25 C-末端发生。使用高渗蔗糖溶液的应用程序，我们发现，容易释放的池的大小保持不变的GABABR激活，但引发的囊泡高渗刺激的敏感性出现降低的响应幅度在中间蔗糖浓度较小，释放动力学减慢。这些数据表明，突触前GABABR可以通过增加囊泡融合的能量屏障直接抑制神经递质的释放。
Neurotransmitter release from presynaptic terminals is under the tight control of various metabotropic receptors. We report here that in addition to the regulation of Ca2+ channel activity, metabotropic GABAB receptors (GABABRs) at murine hippocampal glutamatergic synapses utilize an inhibitory pathway that directly targets the synaptic vesicle release machinery. Acute application of the GABABR agonist baclofen rapidly and reversibly inhibits vesicle fusion, which occurs independently of the SNAP-25 C-terminus. Using applications of hypertonic sucrose solutions, we find that the size of the readily releasable pool remains unchanged by GABABR activation, but the sensitivity of primed vesicles to hypertonic stimuli appears lowered as the response amplitudes at intermediate sucrose concentrations are smaller and release kinetics are slowed. These data show that presynaptic GABABRs can inhibit neurotransmitter release directly by increasing the energy barrier for vesicle fusion.
DOI：
10.1073/pnas.88.17.7834
发表时间：
1991-09-01
影响因子：
11.1
作者：
BEKKERS, JM;STEVENS, CF
通讯作者：
STEVENS, CF
影响因子：
2.5
作者：
Stevens, Charles F.;Williams, James H.
通讯作者：
Williams, James H.
分泌细胞中 Ca 依赖性非分泌囊泡融合。
DOI：
10.1085/jgp.200709950
发表时间：
2008
期刊：
The Journal of general physiology
影响因子：
--
作者：
Wang,Tzu-Ming;Hilgemann,DonaldW
通讯作者：
Hilgemann,DonaldW