Ca v 3.2 T‐type Ca 2+ Channels in H 2 S‐Mediated Hypoxic Response of the Carotid Body

Voltage‐gated Ca 2+ channels (VGCC) are important for carotid body O 2 sensing. We recently reported that Ca v 3.2 is a major T‐Type VGCC isoform expressed in the carotid body, and it contributes to hypoxia‐evoked Ca 2+ influx in glomus cells. Recent studies showed that cystathionine‐γ‐lyase (CSE)‐derived hydrogen sulfide (H 2 S) is a critical mediator of carotid body response to hypoxia. We hypothesized that Ca v 3.2‐dependent carotid body response to hypoxia requires H 2 S. We tested this possibility in wild type (WT) and Ca v 3.2 knockout ( Cacna1h ‐/‐ ) mice. In WT mice, NaHS, a H 2 S donor, like hypoxia, increased [Ca 2+ ] i in glomus cells and carotid body sensory nerve activity, and these responses were markedly reduced in Cacna1h null glomus cells and carotid bodies. To assess the selective role of CSE‐derived H 2 S, studies were performed on WT and CSE ‐/‐ mice. Hypoxia increased [Ca 2+ ] i in glomus cells and this response was attenuated by TTA‐A2, a selective blocker of T‐type VGCC in WT but not in CSE null glomus cells. To determine whether genetic deletion of CSE impaired T‐type VGCC function, CSE null glomus cells were challenged with NaHS. In response to NaHS, [Ca 2+ ] i increased and this effect was inhibited by TTA‐A2 in a reversible manner. Hypoxia‐evoked carotid body sensory nerve excitation was reduced by TTA‐A2 in WT, but not in CSE null carotid bodies. These results demonstrate that Ca v 3.2 T‐type VGCC contribute to H 2 S mediated carotid body response to hypoxia. Supported by NIH HL‐90554.