Role of connexin/pannexin containing channels in infectious diseases

Abstract

In recent years it has become evident that gap junctions and hemichannels, in concert with extracellular ATP and purinergic receptors, play key roles in several physiological processes and pathological conditions. However, only recently has their importance in infectious diseases been explored, likely because early reports indicated that connexin containing channels were completely inactivated under inflammatory conditions, and therefore no further research was performed. However, recent evidence indicates that several infectious agents take advantage of these communication systems to enhance inflammation and apoptosis, as well as to participate in the infectious cycle of several pathogens. In the current review, we will discuss the role of these channels/receptors in the pathogenesis of several infectious diseases and the possibilities of generating novel therapeutic approaches to reduce or prevent these diseases.

Keywords: Bacteria; Gap junction; Purinergic; Virus.

Figure 1

Proposed mechanism by which pathogens use extracellular ATP, uHC and purinergic receptor in the context of infectious diseases. Extracellular and intracellular pathogens bind or activate signaling related to these receptors, leading to ATP release through uHC containing connexin or pannexin proteins. Extracellular ATP binds to specific purinergic receptors, activating calcium influx and G coupled proteins that facilitate intracellular signaling. This signaling participates in inflammation and several pathogens life cycles. In addition, upon release of ATP, several extracellular enzymes degrade ATP into ADP, AMP, and adenosine, which further activate other purinergic and adenosine receptors that participate in inflammation and pathogenesis.