Adenosine stimulates depolarization and rise in cytoplasmic [Ca ] in type I cells of rat carotid bodies

Xu, Fenglian, Jianhua Xu, Frederick W. Tse, and Amy Tse. Adenosine stimulates depolarization and rise in cytoplasmic [Ca ] in type I cells of rat carotid bodies. Am J Physiol Cell Physiol 290: C1592–C1598, 2006. First published January 25, 2006; doi:10.1152/ajpcell.00546.2005.—During hypoxia, the level of adenosine in the carotid bodies increases as a result of ATP catabolism and adenosine efflux via adenosine transporters. Using Ca imaging, we found that adenosine, acting via A2A receptors, triggered a rise in cytoplasmic [Ca ] ([Ca ]i) in type I (glomus) cells of rat carotid bodies. The adenosine response could be mimicked by forskolin (but not its inactive analog), and could be abolished by the PKA inhibitor H89. Simultaneous measurements of membrane potential (perforated patch recording) and [Ca ]i showed that the adenosine-mediated [Ca ]i rise was accompanied by depolarization. Ni , a voltagegated Ca channel (VGCC) blocker, abolished the adenosine-mediated [Ca ]i rise. Although adenosine was reported to inhibit a 4-aminopyridine (4-AP)-sensitive K current, 4-AP failed to trigger any [Ca ]i rise, or to attenuate the adenosine response. In contrast, anandamide, an inhibitor of the TWIK-related acid-sensitive K -1 (TASK-1) channels, triggered depolarization and [Ca ]i rise. The adenosine response was attenuated by anandamide but not by tetraethylammonium. Our results suggest that adenosine, acting via the adenylate cyclase and PKA pathways, inhibits the TASK-1 K channels. This leads to depolarization and activation of Ca entry via VGCC. This excitatory action of adenosine on type I cells may contribute to the chemosensitivity of the carotid body during hypoxia.