Regulation of Ca2+ signals in rat carotid glomus cells

Lei Yan
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 [Ca 2+ ] ([Ca 2+ ] i ) elevation in glomus cells via the activation of voltage-gated Ca 2+ 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
more » ... rial 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 [Ca 2+ ] i measurement (with indo-1), I found that mitochondrial Ca 2+ uptake played a dominant role in cytosolic Ca 2+ clearance in rat glomus cells. Importantly, mitochondrial inhibition increased the duration of the Ca 2+ signal triggered by a voltage-clamped depolarization, which contributed to an enhancement of exocytotic response. Under hypoxic conditions, there was a slowing in cytosolic Ca 2+ clearance, consistent with the scenario that hypoxia caused mitochondrial depolarization and thus reduced mitochondrial Ca 2+ uptake. It has been reported that the hypoxia-triggered CSN discharge is enhanced in the presence of extracellular bicarbonate ion (HCO 3 -). Therefore, in the second project, I investigated the role of HCO 3 in the regulation of Ca 2+ dynamics in glomus cells. Extracellular HCO 3 slowed the rate of cytosolic Ca 2+ clearance in a concentration-dependent manner. Measurement of the mitochondrial Ca 2+ signal with rhod-2 shows that HCO 3 reduced mitochondrial Ca 2+ uptake and this inhibition was abolished in cells treated with scavengers of reactive oxygen species (ROS). Thus, HCO 3 reduced mitochondrial Ca 2+ uptake via a mechanism that was dependent on ROS. Overall, my results show that mitochondrial Ca 2+ uptake in glomus cells could be reduced by hypoxia or by the presence of a physiological concentration of extracellular HCO 3 -. This effect resulted in a slowing in cytosolic Ca 2+ clearance and more transmitter release. The multiplicity of the influences of mitochondria on glomus cell Ca 2+ signaling and exocytosis underscores the importance of mitochondria in hypoxic chemotransduction in the carotid bodies.
doi:10.7939/r30p0x24r fatcat:22fsivqxabb5dbig3xvqhfl7xa