Ca -Induced Ca Release in Aplysia Bag Cell Neurons Requires Interaction Between Mitochondrial and Endoplasmic Reticulum Stores

Geiger JE, Magoski NS. Ca -induced Ca release in Aplysia bag cell neurons requires interaction between mitochondrial and endoplasmic reticulum stores. J Neurophysiol 100: 24–37, 2008. First published May 7, 2008; doi:10.1152/jn.90356.2008. Intracellular Ca is influenced by both Ca influx and release. We examined intracellular Ca following action potential firing in the bag cell neurons of Aplysia californica. Following brief synaptic input, these neuroendocrine cells undergo an afterdischarge, resulting in elevated Ca and the secretion of neuropeptides to initiate reproduction. Cultured bag cell neurons were injected with the Ca indicator, fura-PE3, and subjected to simultaneous imaging and electrophysiology. Delivery of a 5-Hz, 1-min train of action potentials (mimicking the fast phase of the afterdischarge) produced a Ca rise that markedly outlasted the initial influx, consistent with Ca -induced Ca release (CICR). This response was attenuated by about half with ryanodine or depletion of the endoplasmic reticulum (ER) by cyclopiazonic acid. However, depletion of the mitochondria, with carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone, essentially eliminated CICR. Dual depletion of the ER and mitochondria did not reduce CICR further than depletion of the mitochondria alone. Moreover, tetraphenylphosphonium, a blocker of mitochondrial Ca release, largely prevented CICR. The Ca elevation during and subsequent to a stimulus mimicking the full afterdischarge was prominent and enhanced by protein kinase C activation. Traditionally, the ER is seen as the primary Ca source for CICR. However, bag cell neuron CICR represents a departure from this view in that it relies on store interaction, where Ca released from the mitochondria may in turn liberate Ca from the ER. This unique form of CICR may be used by both bag cell neurons, and other neurons, to initiate secretion, activate channels, or induce gene expression.