CaV3.2 T-type Ca²⁺ channels in H₂S-mediated hypoxic response of the carotid body.

Abstract

Arterial blood O2 levels are detected by specialized sensory organs called carotid bodies. Voltage-gated Ca(2+) channels (VGCCs) are important for carotid body O2 sensing. Given that T-type VGCCs contribute to nociceptive sensation, we hypothesized that they participate in carotid body O2 sensing. The rat carotid body expresses high levels of mRNA encoding the α1H-subunit, and α1H protein is localized to glomus cells, the primary O2-sensing cells in the chemoreceptor tissue, suggesting that CaV3.2 is the major T-type VGCC isoform expressed in the carotid body. Mibefradil and TTA-A2, selective blockers of the T-type VGCC, markedly attenuated elevation of hypoxia-evoked intracellular Ca(2+) concentration, secretion of catecholamines from glomus cells, and sensory excitation of the rat carotid body. Similar results were obtained in the carotid body and glomus cells from CaV3.2 knockout (Cacna1h(-/-)) mice. Since cystathionine-γ-lyase (CSE)-derived H2S is a critical mediator of the carotid body response to hypoxia, the role of T-type VGCCs in H2S-mediated O2 sensing was examined. Like hypoxia, NaHS, a H2S donor, increased intracellular Ca(2+) concentration 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 CaV3.2 T-type VGCCs contribute to the H2S-mediated carotid body response to hypoxia.

• Authors: Vladislav V Makarenko, Ying-Jie Peng, Guoxiang Yuan, Aaron P Fox, Ganesh K Kumar, Jayasri Nanduri, Nanduri R Prabhakar
• Journal: American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 308 Issue 2 Pg. C146-54 (Jan 15 2015) ISSN: 1522-1563 [Electronic] United States
• PMID: 25377087 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Calcium Channels
• Calcium Channels, T-Type
• Catecholamines
• Sulfides
• Cystathionine gamma-Lyase
• sodium bisulfide
• Oxygen
• Calcium
• Hydrogen Sulfide

Topics

• Animals
• Calcium (metabolism)
• Calcium Channels (metabolism)
• Calcium Channels, T-Type (metabolism)
• Carotid Body (drug effects, metabolism)
• Catecholamines (metabolism)
• Cells, Cultured
• Chemoreceptor Cells (drug effects, metabolism)
• Cystathionine gamma-Lyase (metabolism)
• Hydrogen Sulfide (pharmacology)
• Hypoxia (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Oxygen (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sulfides