Inositol 1,4,5-Trisphosphate Receptor-Mediated Calcium Release in Purkinje Cells: From Molecular Mechanism to Behavior

Abstract

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.

Endoplasmic reticulum calcium stores in dendritic spines

“…In contrast, GABAergic neurons of the cerebellum contain high concentrations of IP3R, also in dendritic spines. Consequently, IP3Rs were studied extensively in cerebellar purkinje cells (Goto and Mikoshiba, 2011). IP3 stores are important for maintenance of dendritic spine morphology of purkinje cells in the cerebellum (Sugawara et al, 2013).…”

Comparative phenotypic analysis of the two major splice isoforms of phosphatidylinositol phosphate kinase type Iγ in vivo

“…Intracellular Ca 2+ signaling regulates a wide array of neuronal processes (Berridge, 1998). Of particular note is the role of Ca 2+ in Purkinje neurons, where IP 3 -mediated Ca 2+ release from the ER plays a role in long term depression, facilitating motor memory and coordination (Goto and Mikoshiba, 2011). Genetic ablation of other members of the intracellular Ca 2+ release signaling pathway; glutamate receptor mGluR1 (Alba et al, 1994;Conquet et al, 1994), Ga q (Offermanns et al, 1997;Hartmann et al, 2004), PLCb4 (Kim et al, 1997) and IP 3 receptor type 1 (Matsumoto et al, 1996) all result in ataxia and, in some cases, tremors and seizures.…”

The Diversity of Spine Synapses in Animals

“…A similar calcium-regulating function may occur in the complex SER of Purkinje cell spines in the cerebellum. But in this case, it involves IP3 receptors on the spine SER instead of ryanodine receptors (Petralia et al 2001; Goto and Mikoshiba 2011; Segal and Korkotian 2014; Okubo et al 2015) (Fig. 6).…”