Therapeutic Targeting of Connexin Channels: New Views and Challenges

Connexins, in particular connexin 43 (Cx43), function as gap junction channels (GJCs) and hemichannels (HCs). Only recently, specific tools have been developed to study their pleiotropic functions. Based on various protein interaction sites, distinct connexin-mimetic peptides have been established that enable discrimination between the function of HCs and GJCs. Although the precise mechanism of action of most of these peptides is still a matter of debate, an increasing number of studies report on important effects of those compounds in disease models. In this review, we summarize the structure, life cycle, and the most important physiological and pathological functions of both connexin GJCs and HCs. We provide a critical overview on the use of connexin-targeting peptides, in particular targeting Cx43, with a special focus on the remaining questions and hurdles to be taken in the research field of connexin channels.