Inchauspe Carlota González, Martini Francisco J, Forsythe Ian D, Uchitel Osvaldo D
Instituto de Fisiología, Biología Molecular y Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Fisiología, Biología Molecular y Celular, Universidad de Buenos Aires, Argentina.
J Neurosci. 2004 Nov 17;24(46):10379-83. doi: 10.1523/JNEUROSCI.2104-04.2004.
Calcium channels of the P/Q subtype mediate transmitter release at the neuromuscular junction and at many central synapses, such as the calyx of Held. Transgenic mice in which alpha1A channels are ablated provide a powerful tool with which to test compensatory mechanisms at the synapse and to explore mechanisms of presynaptic regulation associated with expression of P/Q channels. Using the calyx of Held preparation from the knock-out (KO) mice, we show here that N-type channels functionally compensate for the absence of P/Q subunits at the calyx and evoke giant synaptic currents [approximately two-thirds of the magnitude of wild-type (WT) responses]. However, although evoked paired-pulse facilitation is prominent in WT, this facilitation is greatly diminished in the KO. In addition, direct recording of presynaptic calcium currents revealed that the major functional difference was the absence of calcium-dependent facilitation at the calyx in the P/Q KO animals. We conclude that one physiological function of P/Q channels is to provide additional facilitatory drive, so contributing to maintenance of transmission as vesicles are depleted during high throughput synaptic transmission.
P/Q亚型钙通道介导神经肌肉接头以及许多中枢突触（如Held壶腹）处的递质释放。α1A通道被敲除的转基因小鼠为测试突触处的代偿机制以及探索与P/Q通道表达相关的突触前调节机制提供了一个强大的工具。利用敲除（KO）小鼠的Held壶腹标本，我们在此表明，N型通道在功能上可代偿Held壶腹处P/Q亚基的缺失，并诱发巨大的突触电流[约为野生型（WT）反应幅度的三分之二]。然而，尽管在WT中诱发的双脉冲易化很明显，但在KO中这种易化作用大大减弱。此外，对突触前钙电流的直接记录显示，主要的功能差异是P/Q KO动物的Held壶腹中不存在钙依赖性易化。我们得出结论，P/Q通道的一个生理功能是提供额外的易化驱动，从而在高流量突触传递过程中囊泡耗尽时有助于维持传递。
