Luminal Ca²⁺dynamics during IP₃R mediated signals

Abstract

The role of cytosolic Ca(2+) on the kinetics of Inositol 1,4,5-triphosphate receptors (IP3Rs) and on the dynamics of IP3R-mediated Ca(2+) signals has been studied at large both experimentally and by modeling. The role of luminal Ca(2+) has not been investigated with that much detail although it has been found that it is relevant for signal termination in the case of Ca(2+) release through ryanodine receptors. In this work we present the results of observing the dynamics of luminal and cytosolic Ca(2+) simultaneously in Xenopus laevis oocytes. Combining observations and modeling we conclude that there is a rapid mechanism that guarantees the availability of free Ca(2+) in the lumen even when a relatively large Ca(2+) release is evoked. Comparing the dynamics of cytosolic and luminal Ca(2+) during a release, we estimate that they are consistent with a 80% of luminal Ca(2+) being buffered. The rapid availability of free luminal Ca(2+) correlates with the observation that the lumen occupies a considerable volume in several regions across the images.

Deterministic Limit of Intracellular Calcium Spikes

“…Considering that open clusters release Ca 2þ at a constant rate Σ [24], the amount of Ca 2þ released depends on the time spent by clusters in state O, which is ruled by the kinetic scheme described above. We evaluate Σ as Σ ¼ I eff × 10 −6 =2V c F, where I eff ¼ Ið1 − bÞ is an effective current accounting for the trapping of a fraction of ions by buffers, F ¼ 96485 C mol −1 is the Faraday constant and the factor 10 −6 ensures that I eff is in picoamperes while Σ is in μM s −1 .…”

Phenomenological cluster-based model of Ca2+ waves and oscillations for inositol 1,4,5-trisphosphate receptor ( IP3R ) channels

“…It is generally known that high Ca 2+ concentrations might lead to cell death and this renders the presence of bistability and consequent sustained Ca 2+ release in our model an unhappy feature. Due to fast luminal Ca 2+ refilling [45] sustained Ca 2+ release, such as what follows from a transition to the upper fixed point of the bistable regime, cannot be terminated by ER depletion at the timescales considered by current paper. The mechanistic origins of our model enable us to propose possible physiological possibilities that might explain the termination of Ca 2+ release from the bistable cluster.…”

“…In this study, we assume the same availability of Ca 2+ in the luminal pool in (4). Even though the ER pool can be large and its fast refilling can prevent local depletion [45], other studies suggest that the large pool can be completely depleted by high-amplitude sustained Ca 2+ releases [49].…”

Changes in Ca2+ Removal Can Mask the Effects of Geometry During IP3R Mediated Ca2+ Signals

“…It does not consider the depletion of the Ca 2+ stores due to the IP 3 R-mediated Ca 2+ release. This might not be that important given that, as analyzed in Lopez and Dawson (2016), luminal Ca 2+ is usually readily available for IP 3 R-mediated release in oocytes. It does not describe either the time during which the signal propagates or the time over which diffusion acts to make [Ca 2+ ] uniform once the release of Ca 2+ stops.…”