Ca2+ homeostasis and exocytosis in carotid glomus cells: Role of mitochondria

In oxygen sensing carotid glomus (type 1) cells, the hypoxia-triggered depolarization can be mimicked by mitochondrial inhibitors. We examined the possibility that, other than causing glomus cell depolarization, mitochondrial inhibition can regulate transmitter release via changes in Ca2+ dynamics. Under whole-cell voltage clamp conditions, application of the mitochondrial inhibitors, carbonyl cyanide m-chlorophenylhydrazone (CCCP) or cyanide caused a dramatic slowing in the decay of the depolarization-triggered Ca2+ signal in glomus cells. In contrast, inhibition of the Na+/Ca2+ exchanger (NCX), plasma membrane Ca2+-ATPase (PMCA) pump or sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) pump had much smaller effects. Consistent with the notion that mitochondrial Ca2+ uptake is the dominant mechanism in cytosolic Ca2+ removal, inhibition of the mitochondrial uniporter with ruthenium red slowed the decay of the depolarization-triggered Ca2+ signal. Hypoxia also slowed cytosolic Ca2+ removal, suggesting a partial impairment of mitochondrial Ca2+ uptake. Using membrane capacitance measurement, we found that the increase in the duration of the depolarization-triggered Ca2+ signal after mitochondrial inhibition was associated with an enhancement of the exocytotic response. The role of mitochondria in the regulation of Ca2+ signal and transmitter release from glomus cells highlights the importance of mitochondria in hypoxic chemotransduction in the carotid bodies.