Gap junction-mimetic peptides do work, but in unexpected ways

Gap junction mimetic peptides containing sequences of the extracellular loops of connexins inhibit the de-novo formation of gap junction channels but do not impair the function of existing cell-cell channels. Recently, a flurry of publications appeared showing that such GAP peptides attenuate ATP release and/or surrogate measures of it. Although no direct effect on putative connexin hemichannels has ever been shown, the peptide effect has been used as diagnostic toot for demonstrating the existence of such channels. However, testing of the peptides on genuine unopposed membrane channels formed by connexins failed to reveal any inhibitory action of the peptides on channel activity. Instead, membrane channels formed by the unrelated pannexin 1 were inhibited in the same concentration range as described for the release of ATP. Consequently, rather than indicating connexin involvement in ATP release, the GAP peptide effects represent Supporting evidence for a role of pannexin 1 in this process.