Two types of functionally distinct Ca2+ stores in hippocampal neurons

Hsing-Jung Chen-Engerer,Jun Yang,Rosa Maria Karl,Jana Hartmann,Stefan Feske,Arthur Konnerth

doi:10.1038/s41467-019-11207-8

Abstract

It is widely assumed that inositol trisphosphate (IP3) and ryanodine (Ry) receptors share the same Ca2+ pool in central mammalian neurons. We now demonstrate that in hippocampal CA1 pyramidal neurons IP3- and Ry-receptors are associated with two functionally distinct intracellular Ca2+ stores, respectively. While the IP3-sensitive Ca2+ store refilling requires Orai2 channels, Ry-sensitive Ca2+ store refilling involves voltage-gated Ca2+ channels (VGCCs). Our findings have direct implications for the understanding of function and plasticity in these central mammalian neurons.

Highlights

CA1 pyramidal neurons IP3- and Ry-receptors are associated with two functionally distinct intracellular Ca2+ stores, respectively
We first analyzed the expression of Orai Ca2+ channels, known to regulate Ca2+ store refilling in non-excitable cells[15,16], in mouse CA1 pyramidal neurons (PNs)
In wild-type (WT) mice, β-gal (5-bromo-4chloro-3-indolyl β-D-galactopyranoside) staining yielded a weak and unspecific staining (Supplementary Fig. 1b, left), whereas a bright signal for β-gal was found in the somatodendritic compartment of CA1 PNs in Orai2−/− mice, confirming both the deletion of the Orai[2] gene in the mutant and its expression in the WT mouse lines, respectively (Supplementary Fig. 1b, right)

Summary

Introduction

CA1 pyramidal neurons IP3- and Ry-receptors are associated with two functionally distinct intracellular Ca2+ stores, respectively. A major source of such neuronal Ca2+ signals is Ca2+ entry from the extracellular space through Ca2+-permeable channels, mostly through voltage-gated Ca2+ channels (VGCCs) in the plasma membrane Another essential source is the intracellular release of Ca2+ ions from endoplasmic reticulum (ER) Ca2+ stores, which is mediated by two types of receptors in the ER membrane, namely, inositoltrisphosphate (IP3) and ryanodine (Ry) receptors[2]. Both IP3 and Ry receptors are abundantly expressed in most central mammalian neurons, including CA1 pyramidal neurons (PNs) and cerebellar Purkinje cells[3]. We set out to investigate the specific roles of Orai[1] and Orai[2] channels for the function(s) of IP3 and Ry receptorsensitive ER Ca2+ stores in CA1 PNs by using Orai-deficient mouse lines

Methods

Results

Conclusion