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Chemical neurotransmission is essential for a variety of neural processes and is traditionally understood to be mediated by Ca2+-dependent exocytosis of synaptic vesicles. Nevertheless, it has been recognized for decades that taste receptor cells in taste buds do not possess synaptic vesicles, yet they can transmit gustatory information to the nervous system. Here I will describe the identification of a unique synapse of taste receptor cells where the ion-conducting pore of a voltage-gated channel, CALHM1/3, serves as the conduit for action potential-dependent neurotransmitter (ATP) release. This mechanism has been termed a ‘channel synapse.’ Anatomically, a channel synapse is characterized by its tripartite structure, which includes a presynaptic mitochondrion adjacent to a CALHM1/3-enriched plasma membrane that faces a post-synaptic afferent nerve. Our recent discoveries extend the roles of channel synapses to various extraoral physiological and pathophysiological processes.