Store‐Operated Ca²⁺ Entry in Oocytes Modulate the Dynamics of IP₃‐Dependent Ca²⁺ Release From Oscillatory to Tonic

Abstract

Ca signaling is ubiquitous and mediates various cellular functions encoded in its spatial, temporal, and amplitude features. Here, we investigate the role of store-operated Ca entry (SOCE) in regulating the temporal dynamics of Ca signals in Xenopus oocytes, which can be either oscillatory or tonic. Oscillatory Ca release from intracellular stores is typically observed at physiological agonist concentration. When Ca release leads to Ca store depletion, this triggers the activation of SOCE that translates into a low-amplitude tonic Ca signal. SOCE has also been implicated in fueling Ca oscillations when activated at low levels. Here, we show that sustained SOCE activation in the presence of IP to gate IP receptors (IP R) results in a pump-leak steady state across the endoplasmic reticulum (ER) membrane that inhibits Ca oscillations and produces a tonic Ca signal. Tonic signaling downstream of SOCE activation relies on focal Ca entry through SOCE ER-plasma membrane (PM) junctions, Ca uptake into the ER, followed by release through open IP Rs at distant sites, a process we refer to as "Ca teleporting." Therefore, sustained SOCE activation in the presence of an IP -dependent "leak" pathway at the ER membrane results in a switch from oscillatory to tonic Ca signaling. J. Cell. Physiol. 232: 1095-1103, 2017. © 2016 Wiley Periodicals, Inc.

Ca2+ tunnelling through the ER lumen as a mechanism for delivering Ca2+ entering via store‐operated Ca2+ channels to specific target sites

“…) and the whole concept has more recently been generalized, based on experiments in oocytes (Courjaret & Machaca, ; Courjaret et al . ). Furthermore, in a recent study (Kar et al .…”

“…We have previously proposed the term ‘Ca 2+ teleporting’ to borrow an analogy from science fiction (Fort, ), to suggest rapid transport of Ca 2+ through the ER lumen given the fact that ER stores are never fully depleted of Ca 2+ (Courjaret et al . ). Although a single Ca 2+ ion is obviously not instantaneously traversing that distance through the ER lumen, the term teleporting nicely reflects the transfer of Ca 2+ from the SOCE entry sites to CaCCs in a directed fashion to modulate CaCC current.…”

“…In addition to modulating the spatial aspects of Ca 2+ signals and effector activation, Ca 2+ tunnelling also modulates the temporal aspects of Ca 2+ signals by favouring tonic over oscillatory Ca 2+ signalling (Courjaret et al . ). When Ca 2+ stores are relatively full, IP 3 production favours Ca 2+ oscillations resulting in repetitive transient Ca 2+ signals.…”

“…In contrast, when SOCE is fully activated with depleted Ca 2+ store, Ca 2+ tunnelling mediates pump–leak balance at the ER membrane that favours tonic sustained Ca 2+ signalling but inhibiting Ca 2+ oscillations (Courjaret et al . ). In this case Ca 2+ tunnelling through the ER lumen targets the IP 3 receptor itself and modulates its properties to favour tonic rather than oscillatory signalling.…”

“…This is indeed the case in the frog oocyte, where IP 3 ‐dependent release of Ca 2+ from the ER fully activates SOCE without emptying the stores completely (Courjaret et al . ).…”