Fig. 1.

Exocytotic versus conductive pathways for export of ATP into extracellular compartments. The top part of the figure illustrates the compartmentalization of ATP and nucleotide-sugars, such as UDP-glucose, into the Golgi apparatus (and endoplasmic reticulum; not shown). Intra-Golgi ATP and nucleotide-sugars play critical roles as substrates for protein-folding chaperones and the enzymes that glycosylate secreted proteins. Residual ATP and nucleotides within the Golgi-derived secretory vesicles are released by the constitutive exocytotic pathways utilized for protein secretion. ATP can be actively accumulated within specialized secretory granules or vesicles that are mobilized during Ca²⁺-dependent regulated exocytosis. Cytosolic ATP can also be released via conductive pathways that involve 1) stimulus-induced gating of various ATP-permeable channels from closed to open states; and/or 2) upregulated trafficking of ATP-permeable channels from intracellular stores to the plasma membrane. The bottom part of the figure illustrates the four major types of channels that can function in conductive ATP release in various cell types. Also shown are the known topographies of individual connexin and pannexin protein subunits and the hexameric states of functional connexin subunit-based hemichannels and pannexin subunit-based channels. The depiction of maxi-anion channels or VRAC-type volume-regulated anion channels as tetrameric assemblies is purely speculative.