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Regulation of Ca2+ signals in rat carotid glomus cells Open Access


Other title
glomus cell
carotid body
Ca2+ imaging
reactive oxygen species
Ca2+ homeostasis
Ca2+ clearance
mitochondrial uniporter
Type of item
Degree grantor
University of Alberta
Author or creator
Yan, Lei
Supervisor and department
Tse, Frederick (Centre for Neuroscience and Department of Pharmacology)
Tse, Amy (Centre for Neuroscience and Department of Pharmacology)
Examining committee member and department
Syed, Naweed (Department of Cell Biology & Anatomy)
Baker, Glen (Centre for Neuroscience and Department of Psychiatry)
Ali, Declan (Centre for Neuroscience and Department of Biological Sciences)
Ballanyi, Klaus (Centre for Neuroscience, Department of Physiology and Department of Pediatrics)
Centre for Neuroscience

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Glomus cells of the carotid body are peripheral chemoreceptors that detect changes in arterial oxygen levels. Hypoxia suppresses oxygen-sensitive K+ channels in glomus cells, resulting in cytosolic [Ca2+] ([Ca2+]i) elevation in glomus cells via the activation of voltage-gated Ca2+ channels. The resultant transmitter release stimulates the carotid sinus nerve (CSN) and the triggering of respiratory and cardiovascular reflexes. Hypoxia also causes mitochondrial depolarization and mitochondrial inhibitors have been shown to cause depolarization in glomus cells via the inhibition of oxygen-sensitive K+ channels. In the first project, with the patch clamp technique in conjunction with [Ca2+]i measurement (with indo-1), I found that mitochondrial Ca2+ uptake played a dominant role in cytosolic Ca2+ clearance in rat glomus cells. Importantly, mitochondrial inhibition increased the duration of the Ca2+ signal triggered by a voltage-clamped depolarization, which contributed to an enhancement of exocytotic response. Under hypoxic conditions, there was a slowing in cytosolic Ca2+ clearance, consistent with the scenario that hypoxia caused mitochondrial depolarization and thus reduced mitochondrial Ca2+ uptake. It has been reported that the hypoxia-triggered CSN discharge is enhanced in the presence of extracellular bicarbonate ion (HCO3-). Therefore, in the second project, I investigated the role of HCO3- in the regulation of Ca2+ dynamics in glomus cells. Extracellular HCO3- slowed the rate of cytosolic Ca2+ clearance in a concentration-dependent manner. Measurement of the mitochondrial Ca2+ signal with rhod-2 shows that HCO3- reduced mitochondrial Ca2+ uptake and this inhibition was abolished in cells treated with scavengers of reactive oxygen species (ROS). Thus, HCO3- reduced mitochondrial Ca2+ uptake via a mechanism that was dependent on ROS. Overall, my results show that mitochondrial Ca2+ uptake in glomus cells could be reduced by hypoxia or by the presence of a physiological concentration of extracellular HCO3-. This effect resulted in a slowing in cytosolic Ca2+ clearance and more transmitter release. The multiplicity of the influences of mitochondria on glomus cell Ca2+ signaling and exocytosis underscores the importance of mitochondria in hypoxic chemotransduction in the carotid bodies.
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Citation for previous publication
Lei Yan, Andy K. Lee, Frederick W. Tse, Amy Tse. (2012).

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