Diseases associated with leaky hemichannels

Abstract

Hemichannels (HCs) and gap junction channels (GJCs) formed by protein subunits called connexins (Cxs) are major pathways for intercellular communication. While HCs connect the intracellular compartment with the extracellular milieu, GJCs allow the interchange of molecules between cytoplasm of two contacting cells. Under physiological conditions, HCs are mostly closed, but they can open under certain stimuli allowing the release of autocrine and paracrine molecules. Moreover, some pathological conditions, like ischemia or other inflammation conditions, significantly increase HCs activity. In addition, some mutations in Cx genes associated with human diseases, such as deafness or cataracts, lead to the formation of more active HCs or “leaky HCs.” In this article we will revise cellular and molecular mechanisms underlying the appearance of leaky HCs, and the consequences of their expression in different cellular systems and animal models, in seeking a common pattern or pathological mechanism of disease.

Connexin43 Mimetic Peptide Improves Retinal Function and Reduces Inflammation in a Light-Damaged Albino Rat Model

“…60 RPE cells under oxidative stress are known to increase the release of basic fibroblast growth factor, which could lead to sustained pathologic angiogenesis in the choroid, 61 and to secrete proinflammatory factors associated with the inflammasome pathways, including Interleukin-1b, Interleukin-6, tumor necrosis factor-a, and granulocyte macrophage-colony stimulating factor. 23,62 In particular, however, capillary dysfunction is reported to precede a number of degenerative CNS diseases, including Alzheimer's and Parkinson's disease [63][64][65] as well as AMD 3-6 and diabetic retinopathy. 2,66 The regulation of Cx43 channels has been shown to protect the vascular bed after retinal ischemia reperfusion and after spinal cord injury, with a corresponding reduction in the inflammatory response, 24,67 and it is of note that in the longer term a reduction in choroid circulation has been reported to be responsible for delayed photoreceptor loss in the light damage model used in this study.…”

Involvement of Gap Junction Proteins in Infectious Diseases Caused by Parasites

“…Trypanosoma cruzi Cardiomyocytes Downregulated [43] Astrocytes Downregulated [44] Leptomeningeal cells Downregulated [44] Cardiomyocytes Downregulated [48] Cardiomyocytes Downregulated [51] Cardiomyocytes and heart human biopsies Downregulated [50] Toxoplasma gondii Astrocytes Downregulated [44] Leptomeningeal cells Downregulated [44] Cx26 Toxoplasma gondii Astrocytes Downregulated [44] Cx37…”

“…The presence and functional HCs in the plasma membrane have been determined through several techniques such as electrophysiology, uptake of fluorescent dyes, and release of adenosine triphosphate (ATP) [44]. Due to the existence of non-selective channels in the plasma membrane, there are significant considerations for studying HCs [45].…”

The GJB2 gene mutation profiles in hearing ımpaired patients from Western Turkey, Canakkale

“…The length of the NT and CT segments is not intended to represent any particular Cx isoform [22,23]. The N-terminal domain plays a role in voltage change by making covalent and non-covalent modifications in an environment surrounded by aminocytes.…”