Inositol 1,4,5-trisphosphate receptor-mediated calcium release in Purkinje cells: from molecular mechanism to...

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.