Cx43G138R leads to an increased activity of ATP-releasing channels. Measurements of ATP concentrations in media of cultured cells expressing Cx43G138R (A and B), and tracer uptake studies (C) showed a doubled activity of ATP-releasing channels. (A) Recombined, heterozygous ES cells expressing the mutation showed an increased activity of the ATP-releasing channels. (B) In oxygen-dependent cardiomyocytes (ED 16.5), the activity of ATP-releasing channels could be observed after 1.5 h of stimulation in a hypoxic incubator, but was not detected in oxygen-independent cells derived from younger embryos (ED 12.5). (C) Studies of tracer uptake of Cx43+/floxG138R:alphaMyHC-Cre cardiomyocytes also indicate the doubled activity of these channels before and after stimulation, as already shown in the ATP-release experiments.