Emerging roles of connexin hemichannels in gastrointestinal and liver pathophysiology

Abstract

Connexin hemichannels have long been considered as mere structural precursors for gap junctions. In the last decade, it has become clear that they also act as individual channels, connecting the intracellular com partment and the extracellular environment. Impaire ment of connexin hemichannel functionality may result in disturbance of homeostasis, as exemplified in the current paper for the intestine and the liver. Research in this field still has a number of shortcomings, of which some are also discussed here.

Gap junctions and non-neoplastic liver disease

“…Further research in this direction is necessary and needs to take into account the possible involvement of new players in the gap junction arena, including hemichannels and pannexin channels. Indeed, hemichannels not only are gap junction building blocks, but also provide a route for communication between the cytoplasm and the extracellular environment [75]. A similar type of channels is formed by pannexins (Panx), that are connexin-like proteins of which three family members have been characterized in humans [76], with Liver tissue from extrahepatic cholestasis patients~ Gap junctions [82,83] Liver tissue from cholelithiasis patients ↓ Gap junctions [84] Liver tissue from rats subjected to bile duct ligation ↓ Gap junctions [27,28] ↓ Gap junctions (ligation) ↑ Gap junctions (recanalization) [29] ↓ Cx32 protein (ligation) ↑ Cx32 protein (recanalization) [33] ↓ Cx32 protein (p38 MAPK-mediated) [32] ↓ GJIC ↓ Cx26 protein ↑ Cx26 mRNA ↓ Cx32 mRNA/protein [30] ↓ Cx26 protein ↓ Cx32 protein ↑ Cx43 protein [31] Liver tissue from rats treated with ethinyl estradiol~ Gap junctions [85] Cx26 protein ↑ Cx32 protein ~ Cx43 protein [31] Liver tissue from rats treated with estradiol valerate ↓ Gap junctions [86] Liver tissue from rats treated with phalloidin ↓ Gap junctions (pericentral) ↓ Cx32 protein [35] ↓ Cx26 protein ↓ Cx32 protein ~ Cx43 protein [31] Liver tissue from cdc42 ↓ Gap junctions [87] Liver tissue from lamprey undergoing biliary atresia ↓ Gap junctions [88] Primary rat hepatocyte doublet cultures exposed to taurolithocholic acid/taurolithocholicsulfate acid/ taurochenodeoxycholic acid ↓ GJIC [36] Normal rat cholangiocyte culture exposed to taurolithocholicsulfate acid ↓ GJIC [36] Liver tissue from rats subjected to choledochocaval fistula -deficient mice Panx1 and Panx2 being expressed in the liver [77].…”

Effects of dietary NEXT ENHANCE®150 on growth performance and expression of immune and intestinal integrity related genes in gilthead sea bream (Sparus aurata L.)

“…Therefore we can only speculate about their differential expression in the two intestinal segments of GSB. What we know about gastrointestinal GJ is that they play a specific role in pacemaking and neurotransmission and thus the regulation of motility in mammals, and some enteric bacteria use these channels for cell invasion [66].…”

Connexin and pannexin (hemi)channels in the liver

“…Hepatocytes, the most prominent liver cell population, directly communicate with each other through gap junctions. The latter are formed by head-to-head docking of 2 hemichannels of neighboring cells, which in turn are composed of 6 connexin (Cx) proteins (Figure 1 ) (Vinken et al, 2006 , 2008 , 2009 , 2010a , b , 2011 ; Decrock et al, 2009 , 2011 ). Historically, these hemichannels have been considered as merely structural precursors of gap junctions.…”