Krapivinsky Grigory, Mochida Sumiko, Krapivinsky Luba, Cibulsky Susan M, Clapham David E
Howard Hughes Medical Institute, Cardiology, Children's Hospital Boston, 1309 Enders Building, 320 Longwood Avenue, Boston, MA, USA.
Neuron. 2006 Nov 9;52(3):485-96. doi: 10.1016/j.neuron.2006.09.033.
A longstanding hypothesis is that ion channels are present in the membranes of synaptic vesicles and might affect neurotransmitter release. Here we demonstrate that TRPM7, a member of the transient receptor potential (TRP) ion channel family, resides in the membrane of synaptic vesicles of sympathetic neurons, forms molecular complexes with the synaptic vesicle proteins synapsin I and synaptotagmin I, and directly interacts with synaptic vesicular snapin. In sympathetic neurons, changes in TRPM7 levels and channel activity alter acetylcholine release, as measured by EPSP amplitudes and decay times in postsynaptic neurons. TRPM7 affects EPSP quantal size, an intrinsic property of synaptic vesicle release. Targeted peptide interference of TRPM7's interaction with snapin affects the amplitudes and kinetics of postsynaptic EPSPs. Thus, vesicular TRPM7 channel activity is critical to neurotransmitter release in sympathetic neurons.
一个长期存在的假说认为,离子通道存在于突触小泡膜中,可能会影响神经递质的释放。在这里,我们证明瞬时受体电位(TRP)离子通道家族的成员TRPM7存在于交感神经元突触小泡膜中,与突触小泡蛋白突触素I和突触结合蛋白I形成分子复合物,并直接与突触小泡Snapin相互作用。在交感神经元中,通过测量突触后神经元的兴奋性突触后电位(EPSP)幅度和衰减时间发现,TRPM7水平和通道活性的变化会改变乙酰胆碱的释放。TRPM7影响EPSP量子大小,这是突触小泡释放的一个内在特性。TRPM7与Snapin相互作用的靶向肽干扰会影响突触后EPSP的幅度和动力学。因此,囊泡TRPM7通道活性对交感神经元中神经递质的释放至关重要。