Introduction: connexins, pannexins and their channels as gatekeepers of organ physiology

Homeostasis relies on the intimate interplay between extracellular, intracellular and intercellular signaling networks. Direct communication between adjacent cells is mediated by gap junctions [1-3]. They allow the intercellular diffusion of small (i.e. less than 1 kDa) and hydrophilic substances, including adenosine triphosphate (ATP), cyclic adenosine monophosphate, inositol triphosphate, glucose, glutathione, glutamate and several ions, like sodium, calcium and potassium (Fig. 1) [4]. This flux is called gap junctional intercellular communication (GJIC) and is considered as a basic mechanism in the maintenance of tissue functioning [1-3]. Over the last decades, GJIC has been shown indispensable for the establishment of metabolic or electrical intercellular coupling in all vital organs, such as the brain [5], the heart [6] and the liver [7], to name a few.