Yasuda Ryohei, Sabatini Bernardo L, Svoboda Karel
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road Cold Spring Harbor, New York 11724, USA.
Nat Neurosci. 2003 Sep;6(9):948-55. doi: 10.1038/nn1112.
Voltage-sensitive Ca2+ channels (VSCCs) constitute a major source of calcium ions in dendritic spines, but their function is unknown. Here we show that R-type VSCCs in spines of rat CA1 pyramidal neurons are depressed for at least 30 min after brief trains of back-propagating action potentials. Populations of channels in single spines are depressed stochastically and synchronously, independent of channels in the parent dendrite and other spines, implying that depression is the result of signaling restricted to individual spines. Induction of VSCC depression blocks theta-burst-induced long-term potentiation (LTP), indicating that postsynaptic action potentials can modulate synaptic plasticity by tuning VSCCs. Induction of depression requires [Ca2+] elevations and activation of L-type VSCCs, which activate Ca2+/calmodulin-dependent kinase II (CaMKII) and a cyclic adenosine monophosphate (cAMP)-dependent pathway. Given that L-type VSCCs do not contribute measurably to Ca2+ influx in spines, they must activate downstream effectors either directly through voltage-dependent conformational changes or via [Ca2+] microdomains.
电压敏感性Ca2+通道（VSCCs）是树突棘中钙离子的主要来源，但它们的功能尚不清楚。我们在此表明，大鼠CA1锥体神经元树突棘中的R型VSCCs在短暂的反向传播动作电位串刺激后至少30分钟内受到抑制。单个树突棘中的通道群体随机且同步地受到抑制，独立于母树突和其他树突棘中的通道，这意味着抑制是限于单个树突棘的信号传导的结果。VSCC抑制的诱导会阻断theta爆发诱导的长期增强（LTP），表明突触后动作电位可通过调节VSCCs来调节突触可塑性。抑制的诱导需要[Ca2+]升高和L型VSCCs的激活，后者激活Ca2+/钙调蛋白依赖性激酶II（CaMKII）和环磷酸腺苷（cAMP）依赖性途径。鉴于L型VSCCs对树突棘中Ca2+内流的贡献微不足道，它们必须通过电压依赖性构象变化或通过[Ca2+]微区直接激活下游效应器。
