Oxygen and carotid body chemotransduction: the cholinergic hypothesis - a brief history and new evaluation

Oxygen can be said to be the most fundamentally necessary substrate for life. In those organisms having a cardiopulmonary system for delivering it in blood to the tissues the carotid body functions as the principal detector of decreases in arterial oxygen. Such a decrease stimulates an increase in neural output from the carotid body to the nucleus tractus solitarii, and this can precipitate a wide array of systemic reflex responses. The neural mechanisms involved in the genesis of increased signal from the carotid body remain unclear. But a current model of carotid body chemotransduction postulates that transmitter-laden glomus cells initiate the neural activity by being depolarized by hypoxemia and releasing an excitatory transmitter which binds to postsynaptic receptors of the adjacent sensory afferent fibers as well as to presynaptic glomus cell autoreceptors. This Frontiers Review evaluates anew the data supporting the hypothesis that acetylcholine (ACh) is an (the) essential excitatory transmitter in this process by examining ACh's fulfillment of criteria required to establish a substance as a synaptic transmitter. All eight criteria are fulfilled in the case of ACh. Indeed, additional data further support the Cholinergic Hypothesis.