Arterial blood oxygen (O2) levels are detected by specialized sensory organs called carotid bodies. Voltage-gated Ca2+ channels (VGCC) are important for carotid body O2 sensing. Given that T-type VGCC contributes to nociceptive sensation, we hypothesized that they participate in carotid body O2 sensing. The rat carotid body expresses high levels of mRNA encoding α1H subunit and α1H protein is localized to glomus cells, the primary O2 sensing cells in the chemoreceptor tissue suggesting that CaV 3.2 is the major T-Type VGCC isoform expressed in the carotid body. Mibefradil and TTA-A2, selective blockers of T-type VGCC, markedly attenuated hypoxia-evoked [Ca2+]i elevation, catecholamine (CA) secretion from glomus cells and sensory excitation of the rat carotid body. Similar results were also obtained in the carotid body and glomus cells from CaV 3.2 knockout mice (Cacna1h-/-). Since cystathionine-γ-lyase (CSE)-derived hydrogen sulfide (H2S) is a critical mediator of carotid body response to hypoxia, the role of T-type VGCC in H2S-mediated O2 sensing was examined. Like hypoxia, NaHS, a H2S donor increased [Ca2+]i and augmented carotid body sensory nerve activity in wild type mice and these effects were markedly attenuated in Cacna1h-/- mice. In wild type mice, TTA-A2 markedly attenuated glomus cell and carotid body sensory nerve responses to hypoxia and these effects were absent in CSE knockout mice. These results demonstrate that CaV 3.2 T-type VGCC contribute to H2S mediated carotid body response to hypoxia.
- O2 sensing
- Voltage-gated Ca2+ channels
- T-type Ca2+ channel
- Carotid body
- Copyright © 2014, American Journal of Physiology - Cell Physiology