Connexin and pannexin (hemi)channels in the liver

Abstract

The liver was among the first organs in which connexin proteins have been identified. Hepatocytes harbor connexin32 and connexin26, while non-parenchymal liver cells typically express connexin43. Connexins give rise to hemichannels, which dock with counterparts on adjacent cells to form gap junctions. Both hemichannels and gap junctions provide pathways for communication, via paracrine signaling or direct intercellular coupling, respectively. Over the years, hepatocellular gap junctions have been shown to regulate a number of liver-specific functions and to drive liver cell growth. In the last few years, it has become clear that connexin hemichannels are involved in liver cell death, particularly in hepatocyte apoptosis. This also holds true for hemichannels composed of pannexin1, a connexin-like protein recently identified in the liver. Moreover, pannexin1 hemichannels are key players in the regulation of hepatic inflammatory processes. The current paper provides a concise overview of the features of connexins, pannexins and their channels in the liver.

Lipoapoptosis induced by saturated free fatty acids stimulates monocyte migration: a novel role for Pannexin1 in liver cells

“…One explanation for this discrepancy may be that Panx1 shRNAs or YoPro-1 concentrations used here were not optimal. Based on our recent work and the literature, there are several mechanisms for eATP release and YoPro-1 uptake in liver cells [48][49][50]. Although Panx1 can act in a receptor-independent fashion, it is equally possible that Panx1 pore formation is operating by a P2X7 receptor-driven mechanism [51][52][53].…”

Connexin hemichannel inhibition reduces acetaminophen-induced liver injury in mice

“…The latter can be mediated by gap junctions, a group of cell-to-cell contacts composed of 2 hemichannels of adjacent cells, which in turn are built up by 6 connexin (Cx) proteins (Maes et al, 2014; Vinken et al, 2008). At present, 21 connexin proteins have been identified in humans, while in rodents 20 connexin proteins have been characterized.…”

Connexin32: a mediator of acetaminophen-induced liver injury?

“…Unlike GJIC, hemichannel signaling occurs between the cytoplasm of individual cells and their extracellular environment. While gap junctions may be involved both in physiological and pathological processes, hemichannels seem to be consistently associated with the latter (Decrock et al 2009; Maes et al 2014; Vinken et al 2010). In fact, connexin signaling has been causally linked to liver disease and toxicity (Vinken et al 2009).…”