After Ca2+ influx, mitochondria can sequester Ca2+ and subsequently release it back into the cytosol. This form of Ca2+-induced Ca2+ release (CICR) prolongs Ca2+ signaling and can potentially mediate activity-dependent plasticity. As Ca2+ is required for its subsequent release, Ca2+ removal systems, like the plasma membrane Ca2+-ATPase (PMCA), could impact CICR. Here we examine such a role for the PMCA in the bag cell neurons of Aplysia californica. CICR is triggered in these neurons during an afterdischarge and is implicated in sustaining membrane excitability and peptide secretion. Somatic Ca2+ was measured from fura-PE3-loaded cultured bag cell neurons recorded under whole cell voltage clamp. Voltage-gated Ca2+ influx was elicited with a 5-Hz, 1-min train, which mimics the fast phase of the afterdischarge. PMCA inhibition with carboxyeosin or extracellular alkalization augmented the effectiveness of Ca2+ influx in eliciting mitochondrial CICR. A Ca2+ compartment model recapitulated these findings and indicated that disrupting PMCA-dependent Ca2+ removal increases CICR by enhancing mitochondrial Ca2+ loading. Indeed, carboxyeosin augmented train-evoked mitochondrial Ca2+ uptake. Consistent with their role on Ca2+ dynamics, cell labeling revealed that the PMCA and mitochondria overlap with Ca2+ entry sites. Finally, PMCA-dependent Ca2+ extrusion did not impact endoplasmic reticulum-dependent Ca2+ removal or release, despite the organelle residing near Ca2+ entry sites. Our results demonstrate that Ca2+ removal by the PMCA influences the propensity for stimulus-evoked CICR by adjusting the amount of Ca2+ available for mitochondrial Ca2+ uptake. This study highlights a mechanism by which the PMCA could impact activity-dependent plasticity in the bag cell neurons.
- Aplysia californica
- Ca2+-induced Ca2+ release
- neuroendocrine cells
- voltage-gated Ca2+ channels
- Ca2+ buffering
- Copyright © 2016 the American Physiological Society
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