Producción CientíficaChromaffin cells are an excellent model for stimulus–
secretion coupling. Ca2+ entry through plasma membrane
voltage-operated Ca2+ channels (VOCC) is the trigger
for secretion, but the intracellular organelles contribute subtle
nuances to the Ca2+ signal. The endoplasmic reticulum
amplifies the cytosolic Ca2+ ([Ca2+]C) signal by Ca2+-
induced Ca2+ release (CICR) and helps generation of microdomains
with high [Ca2+]C (HCMD) at the subplasmalemmal
region. These HCMD induce exocytosis of the docked
secretory vesicles. Mitochondria close to VOCC take up
large amounts of Ca2+ from HCMD and stop progression
of the Ca2+ wave towards the cell core. On the other hand,
the increase of [Ca2+] at the mitochondrial matrix stimulates
respiration and tunes energy production to the increased
needs of the exocytic activity. At the end of stimulation,
[Ca2+]C decreases rapidly and mitochondria release the Ca2+
accumulated in the matrix through the Na+/Ca2+ exchanger.
VOCC, CICR sites and nearby mitochondria form functional
triads that co-localize at the subplasmalemmal area, where
secretory vesicles wait ready for exocytosis. These triads
optimize stimulus–secretion coupling while avoiding
propagation of the Ca2+ signal to the cell core. Perturbation
of their functioning in neurons may contribute to the genesis
of excitotoxicity, ageing mental retardation and/or neurodegenerative
disorders
