The type I cells are the chemoreceptive elements of the carotid bodies and are critical in defining the ventilatory response to hypoxia and hypercapnia. Recent evidence has suggested that histamine is released by the carotid body in response to hypoxia and acts as an excitatory neurotransmitter. Here we use isolated neonatal rat type I cells to assess the presynaptic actions of histamine and define the receptor subtypes that mediate them. All four histamine receptor subtypes are expressed on the type I cells, however activation of these receptors with histamine or selective agonists caused no rise in intracellular calcium ([Ca2+]i) and histamine did not augment calcium entry or modulate macroscopic currents evoked in type I cells.

Thus activation of histamine receptors on type I cells is unlikely to provide a presynaptic positive feedback mechanism during chemotransduction and any excitatory role attributed to the actions of histamine is likely to come from a postsynaptic effect on the carotid sinus nerve (CSN).