During hypoxia, the level of adenosine in the carotid bodies increases as a result of ATP catabolism and adenosine efflux via adenosine transporters. Using Ca²⁺ imaging, we found that adenosine, acting via A_2A receptors, triggered a rise in cytoplasmic [Ca²⁺] ([Ca²⁺]_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 protein kinase A (PKA) inhibitor, H89. Simultaneous measurements of membrane potential (perforated patch recording) and [Ca²⁺]_i showed that the adenosine-mediated [Ca²⁺]_i rise was accompanied by depolarization. Ni²⁺, a voltage-gated Ca²⁺ channel (VGCC) blocker abolished the adenosine-mediated [Ca²⁺]_i rise. Although adenosine was reported to inhibit a 4-aminopyridine (4-AP) sensitive K⁺ current, 4-AP failed to trigger any [Ca²⁺]_i rise or to attenuate the adenosine response. In contrast, anandamide, an inhibitor of the TASK-1 K⁺ channels triggered depolarization and [Ca²⁺]_i rise. The adenosine response was attenuated by anandamide, but not by tetraethylammonium (TEA). Our results suggest that adenosine, acting via the adenylate cyclase and PKA pathway, inhibits the TASK-1 K⁺ channels. This leads to depolarization and activation of Ca²⁺ entry via VGCC. This excitatory action of adenosine on type I cells may contribute to the chemosensitivity of the carotid body during hypoxia.