Ca2+ removal by the plasma membrane Ca2+-ATPase influences the contribution of mitochondria to activity-dependent Ca2+ dynamics in Aplysia neuroendocrine cells

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 i...