Figure 7. Schematic representation of the role of purinergic signalling mechanisms in cell–cell interactions at the rat carotid body ‘tripartite’ synapse .

The chemostimuli hypoxia and hypercapnia depolarize type I cells through inhibition of TASK1/3 K⁺ channels (1), leading to Ca²⁺ entry through voltage‐gated Ca²⁺ channels (VGCC) and ATP release (2). ATP stimulates postsynaptic P2X2/3 receptors on petrosal afferent nerve terminals causing excitation, as well as P2Y2 receptors (P2Y2R) on adjacent glial‐like type II cells. P2Y2R stimulation leads to Ca²⁺ release from intracellular stores via inositol trisphosphate (IP₃) signalling pathways and opening of pannexin‐1 channels, allowing further release of ATP into the synaptic cleft. ATP (from both type II and type I cells) is broken down by extracellular 5′‐ectonucleotidase (5′ENT) into adenosine (ADO) (3), which activates primarily ADO A_2A receptors (A_2AR) on type I cells. Activation of A_2A receptors leads to inhibition of TASK1/3 channels to further enhance type I cell depolarization (4) (Xu et al. 2006), and therefore ATP release. Omitted for clarity is the pathway by which hypoxia stimulates ADO release from type I cells via a plasma membrane nucleoside transporter, and negative feedback pathways by which ATP inhibits type I cells via P2Y1 receptors (Xu et al. 2005) and pannexin‐1 channels in type II cells (Nurse, 2014).