Gap junctions communicate and coordinate the activity of neighbouring cells. They have been found in various cells types such as cardiomyocytes, smooth muscle fibres, epithelial cells and astrocytes. Communication between the cytoplasm of adjacent cells is established through an aqueous pore. Each cell contributes half the intercellular channel. Each moiety is known as a connexon, a hemichannel or a gap junction hemichannel. Hemichannels can be found in the plasma membrane alone representing some intermediate step in the turnover of gap junctions. However, some authors suggest they may have a physiological role. In astrocytes, experimental evidence suggests that hemichannels contribute to communication between cells by releasing ATP, which in turn activates purinergic receptors and eventually generates a propagating calcium wave. Probably the most frequent cell pathway of ATP release is the exocytosis of vesicles or granules, although hemichannels are theoretically permeable to ATP. We have examined the direct role of connexins in the release of ATP, using Xenopus oocytes. They contain a particular kind of connexin called Cx38, which forms hemichannels that are activated by physiological solutions devoid of divalent cations. When Cx38 is activated, we find a release of ATP, which is dependent on the level of expression of Cx38 and is sensitive to gap junction blockers. The activity of Cx38 hemichannels can be modulated by other membrane proteins; for example, it is inhibited by syntaxin 1A, a SNARE protein. Syntaxin forms complexes that control vesicle exocytosis, but also modulates the activity of voltage-dependent calcium channels and CFTR-supported chloride currents. Moreover, mutations in human connexins have been related to certain disorders. X-linked Charcot Marie Tooth disease has been related to mutations in Cx32, and a form of deafness is related to Cx26. By combining the two electrode voltage clamp technology and the use of luciferin-luciferase reaction in single Xenopus oocytes, we have simultaneously measured the activation of Cx32 and ATP release. In oocytes transfected with Cx32 cRNA, the release of ATP was associated with a tail current when oocytes were depolarized. In addition, Cx32 hemichannel activity is sensitive to the extracellular calcium concentration. Indeed, both the current and the amount of ATP released were higher when the oocytes were depolarized in solutions with low calcium concentration. All these results strongly support the view that ATP is released through hemichannels in certain conditions. Changes in the permeability of hemichannels may raise the extracellular concentration of ATP, surpassing a toxic threshold that may induce cell death and pathological alterations.