Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, WA 98195, USA.
Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17069-74. doi: 10.1073/pnas.1215172109. Epub 2012 Oct 1.
Modulation of P/Q-type Ca(2+) currents through presynaptic voltage-gated calcium channels (Ca(V)2.1) by binding of Ca(2+)/calmodulin contributes to short-term synaptic plasticity. Ca(2+)-binding protein-1 (CaBP1) and Visinin-like protein-2 (VILIP-2) are neurospecific calmodulin-like Ca(2+) sensor proteins that differentially modulate Ca(V)2.1 channels, but how they contribute to short-term synaptic plasticity is unknown. Here, we show that activity-dependent modulation of presynaptic Ca(V)2.1 channels by CaBP1 and VILIP-2 has opposing effects on short-term synaptic plasticity in superior cervical ganglion neurons. Expression of CaBP1, which blocks Ca(2+)-dependent facilitation of P/Q-type Ca(2+) current, markedly reduced facilitation of synaptic transmission. VILIP-2, which blocks Ca(2+)-dependent inactivation of P/Q-type Ca(2+) current, reduced synaptic depression and increased facilitation under conditions of high release probability. These results demonstrate that activity-dependent regulation of presynaptic Ca(V)2.1 channels by differentially expressed Ca(2+) sensor proteins can fine-tune synaptic responses to trains of action potentials and thereby contribute to the diversity of short-term synaptic plasticity.
通过与钙调蛋白（CaM）结合，调节突触前电压门控钙通道（CaV2.1）中的 P/Q 型 Ca2+电流，从而促进短期突触可塑性。钙结合蛋白-1（CaBP1）和视蛋白样蛋白-2（VILIP-2）是神经特异性的 CaM 样 Ca2+传感器蛋白，它们可以差异化地调节 CaV2.1 通道，但它们如何促进短期突触可塑性尚不清楚。本研究表明，CaBP1 和 VILIP-2 对 CaV2.1 通道的活动依赖性调节对颈上交感神经节神经元的短期突触可塑性具有相反的影响。表达 CaBP1 可阻断 P/Q 型 Ca2+电流的 Ca2+依赖性易化，从而显著减少突触传递的易化。VILIP-2 可阻断 P/Q 型 Ca2+电流的 Ca2+依赖性失活，在高释放概率条件下，VILIP-2 减少了突触抑制，增加了易化。这些结果表明，通过差异表达的 Ca2+传感器蛋白对突触前 CaV2.1 通道的活动依赖性调节可以微调对动作电位串的突触反应，从而有助于短期突触可塑性的多样性。
