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 Ca(2+) 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 Ca(2+) signal in glomus cells. In contrast, inhibition of the Na(+)/Ca(2+) exchanger (NCX), plasma membrane Ca(2+)-ATPase (PMCA) pump or sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump had much smaller effects. Consistent with the notion that mitochondrial Ca(2+) uptake is the dominant mechanism in cytosolic Ca(2+) removal, inhibition of the mitochondrial uniporter with ruthenium red slowed the decay of the depolarization-triggered Ca(2+) signal. Hypoxia also slowed cytosolic Ca(2+) removal, suggesting a partial impairment of mitochondrial Ca(2+) uptake. Using membrane capacitance measurement, we found that the increase in the duration of the depolarization-triggered Ca(2+) signal after mitochondrial inhibition was associated with an enhancement of the exocytotic response. The role of mitochondria in the regulation of Ca(2+) signal and transmitter release from glomus cells highlights the importance of mitochondria in hypoxic chemotransduction in the carotid bodies.
Center for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.
Lei
L
Yan
Andy K
AK
Lee
Frederick W
FW
Tse
Amy
A
Tse
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002344:Carotid Body / Q000166:cytology / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D003486:Cyanides / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D053499:Plasma Membrane Calcium-Transporting ATPases; D061209:Proton Ionophores / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism
D003486:Cyanides; D009419:Nerve Tissue Proteins; D061209:Proton Ionophores; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D053499:Plasma Membrane Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium