Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama, Japan.
Cerebellum. 2011 Dec;10(4):820-33. doi: 10.1007/s12311-011-0270-5.
The inositol 1,4,5-trisphosphate (IP(3)) receptor is highly expressed in cerebellar Purkinje cells and mediates conspicuous calcium release from intracellular calcium stores. Receptor stimulation, such as through mGluR1, activates the G(q)-PLC pathway, which leads to IP(3)-induced calcium release and subsequent cellular responses, including cerebellar long-term depression in Purkinje cells. Recent studies have demonstrated the regulatory mechanisms of IP(3) receptor, revealing activation via IP(3) and Ca(2+), inactivation via high concentrations of Ca(2+), and modulation by various proteins that bind to the IP(3) receptor. Novel calcium imaging techniques and caged compounds provide analysis of calcium signals at the single spine level in relation to the induction of long-term depression. Genetically encoded indicators for calcium or IP(3) could provide alternate Ca(2+) or IP(3) imaging, in particular, for in vivo observations. IP(3)-induced calcium release participates in early development of dendritic branch formation, and loss-of-function mutations or hyper-activation could result various diseases. The IP(3) receptor plays a central role in calcium signaling in Purkinje cells, affecting a wide variety of cellular functions, including development, plasticity, maintenance of synaptic functions, and cerebellar motor control.
三磷酸肌醇（IP（3））受体在小脑浦肯野细胞中高度表达，并介导细胞内钙库中明显的钙释放。受体刺激，如通过 mGluR1，激活 G(q)-PLC 途径，导致 IP（3）诱导的钙释放和随后的细胞反应，包括浦肯野细胞中的小脑长时程抑制。最近的研究表明了 IP（3）受体的调节机制，揭示了通过 IP（3）和 Ca（2+）的激活、通过高浓度 Ca（2+）的失活以及与 IP（3）受体结合的各种蛋白质的调节。新型钙成像技术和笼状化合物提供了与长时程抑制诱导相关的单个棘突水平钙信号的分析。用于钙或 IP（3）的基因编码指示剂可以提供替代的 Ca（2+）或 IP（3）成像，特别是用于体内观察。IP（3）诱导的钙释放参与树突分支形成的早期发育，功能丧失突变或过度激活可能导致各种疾病。IP（3）受体在浦肯野细胞中的钙信号中起核心作用，影响广泛的细胞功能，包括发育、可塑性、突触功能的维持和小脑运动控制。
