Role Of Connexins Research Articles

The Role of the Gap Junction Protein Connexin in Adrenal Gland Tumorigenesis.

Gap junctions (GJs) are important in the regulation of cell growth, morphology, differentiation and migration. However, recently, more attention has been paid to their role in the pathogenesis of different diseases as well as tumorigenesis, invasion and metastases. The expression pattern and possible role of connexins (Cxs), as major GJ proteins, under both physiological and pathological conditions in the adrenal gland, were evaluated in this review. The databases Web of Science, PubMed and Scopus were searched. Studies were evaluated if they provided data regarding the connexin expression pattern in the adrenal gland, despite current knowledge of this topic not being widely investigated. Connexin expression in the adrenal gland differs according to different parts of the gland and depends on ACTH release. Cx43 is the most studied connexin expressed in the adrenal gland cortex. In addition, Cx26, Cx32 and Cx50 were also investigated in the human adrenal gland. Cx50 as the most widespread connexin, along with Cx26, Cx29, Cx32, Cx36 and Cx43, has been expressed in the adrenal medulla with distinct cellular distribution. Considerable effort has recently been directed toward connexins as therapeutically targeted molecules. At present, there exist several viable strategies in the development of potential connexin-based therapeutics. The differential and hormone-dependent distribution of gap junctions within adrenal glands, the relatively large gap junction within this gland and the increase in the gap junction size and number following hormonal treatment would indicate that gap junctions play a pivotal role in cell functioning in the adrenal gland.

Connexin 43 Prevents Radiation-Induced Intestinal Damage via the Ca2+-Dependent PI3K/Akt Signaling Pathway.

Radiation-induced intestinal damage (RIID) is a common side effect of radiotherapy in patients with abdominopelvic malignancies. Gap junctions are special structures consisting of connexins (Cxs). This study aimed to investigate the expression and role of connexins in RIID and underlying mechanism. In this study, a calcein-AM fluorescence probe was used to detect changes in gap junctional intercellular communication in intestinal epithelial IEC-6 cells. Our results show that gap junctional intercellular communication of IEC-6 cells was reduced at 6, 12, 24, and 48 h after irradiation, with the most pronounced effect at 24 h. Western blotting and immunofluorescence results showed that the expression of Cx43, but not other connexins, was reduced in irradiated intestinal epithelial cells. Silencing of Cx43 reduced gap junctional intercellular communication between irradiated intestinal epithelial cells with increased ROS and intracellular Ca2+ levels. Furthermore, knockdown of Cx43 reduced the number of clonal clusters, decreased cell proliferation with increased cytotoxicity and apoptosis. Western blotting results showed that silencing of Cx43 resulted in changed γ-H2AX and PI3K/AKT pathway proteins in irradiated intestinal epithelial cells. Administration of the PI3K/AKT pathway inhibitor LY294002 inhibited the radioprotective effects in Cx43-overexpressing intestinal epithelial cells. Our study demonstrated that Cx43 expression is decreased by ionizing radiation, which facilitates the radioprotection of intestinal epithelial cells.

The Role of Connexin in Ophthalmic Neovascularization and the Interaction between Connexin and Proangiogenic Factors

The formation of new blood vessels is an important physiological process that occurs during development. When the body is injured, new blood vessel formation helps the body recuperate by supplying more oxygen and nutrients. However, this mechanism can have a negative effect. In ophthalmologic diseases, such as corneal new blood vessels, neonatal vascular glaucoma, and diabetes retinopathy, the formation of new blood vessels has become a critical component in patient survival. Connexin is a protein that regulates the cellular and molecular material carried by cells. It has been demonstrated that it is widely expressed in vascular endothelial cells, where it forms a slit connection between adjacent cells to promote cell-cell communication via hemichannels, as well as substance exchange into intracellular environments. Numerous studies have demonstrated that connexin in vascular endothelial cells plays an important role in angiogenesis and vascular leakage. The purpose of this study was to investigate the effect between the angiogenesis-associated factor and the connexin. It also reveals the effect of connexin on ophthalmic neovascularization.

Mechanisms of SARS-CoV-2 and Male Infertility: Could Connexin and Pannexin Play a Role?

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male infertility has lately received significant attention. SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) in humans, has been shown to impose adverse effects on both the structural components and function of the testis, which potentially impact spermatogenesis. These adverse effects are partially explained by fever, systemic inflammation, oxidative stress, and an increased immune response leading to impaired blood-testis barrier. It has been well established that efficient cellular communication via gap junctions or functional channels is required for tissue homeostasis. Connexins and pannexins are two protein families that mediate autocrine and paracrine signaling between the cells and the extracellular environment. These channel-forming proteins have been shown to play a role in coordinating cellular communication in the testis and epididymis. Despite their role in maintaining a proper male reproductive milieu, their function is disrupted under pathological conditions. The involvement of these channels has been well documented in several physiological and pathological conditions and their designated function in infectious diseases. However, their role in COVID-19 and their meaningful contribution to male infertility remains to be elucidated. Therefore, this review highlights the multivariate pathophysiological mechanisms of SARS-CoV-2 involvement in male reproduction. It also aims to shed light on the role of connexin and pannexin channels in disease progression, emphasizing their unexplored role and regulation of SARS-CoV-2 pathophysiology. Finally, we hypothesize the possible involvement of connexins and pannexins in SARS-CoV-2 inducing male infertility to assist future research ideas targeting therapeutic approaches.

Connexin45 colocalization patterns in the plexiform layers of the developing mouse retina.

Chemical and electrical synapses (gap junctions) are widely prevalent in the nervous system. Gap junctions emerge long before chemical synapses, allowing communication between developing cells, and are thought to be involved in establishing neural circuits. Mounting evidence indicates that these two modalities of synaptic transmission closely interact during retinal development and that such interactions play a critical role in synaptogenesis and circuit formation during the perinatal period. In vertebrates, gap junctions consist of two connexins which in turn are made up of six connexins (Cx). To what extent Cx45 and Cx36, the most abundant connexins in the retina, are involved in synaptogenesis and retinal circuit formation is not known. The here presented immunohistochemical study used stainings of Cx45, Cx36 and Synaptophysin in the outer and inner (IPL) plexiform layers of postnatal day 8-16 mice retinas to shed light on the role of connexins during critical neuronal developmental processes. Cx45 and Cx36 expressions in both plexiform layers of the mouse retina increased till eye opening and dropped afterwards. The percentage of heterotypic Cx45/Cx36 gap junctions is also higher before the critical event of eye opening. Finally, Cx45 is closely located and/or colocalized with Synaptophysin also shortly before eye opening in the IPL of the mouse retina. All findings point towards a pivotal role for Cx45 during postnatal synaptogenesis in the mouse retina. However, a more functional study is needed to determine the role of Cx45 during synaptogenesis and circuit formation.

New Insights on the Role of Connexins and Gap Junctions Channels in Adipose Tissue and Obesity.

Due to the inability to curb the excessive increase in the prevalence of obesity and overweight, it is necessary to comprehend in more detail the factors involved in the pathophysiology and to appreciate more clearly the biochemical and molecular mechanisms of obesity. Thus, understanding the biological regulation of adipose tissue is of fundamental relevance. Connexin, a protein that forms intercellular membrane channels of gap junctions and unopposed hemichannels, plays a key role in adipogenesis and in the maintenance of adipose tissue homeostasis. The expression and function of Connexin 43 (Cx43) during the different stages of the adipogenesis are differentially regulated. Moreover, it has been shown that cell–cell communication decreases dramatically upon differentiation into adipocytes. Furthermore, inhibition of Cx43 degradation or constitutive overexpression of Cx43 blocks adipocyte differentiation. In the first events of adipogenesis, the connexin is highly phosphorylated, which is likely associated with enhanced Gap Junction (GJ) communication. In an intermediate state of adipocyte differentiation, Cx43 phosphorylation decreases, as it is displaced from the membrane and degraded through the proteasome; thus, Cx43 total protein is reduced. Cx is involved in cardiac disease as well as in obesity-related cardiovascular diseases. Different studies suggest that obesity together with a high-fat diet are related to the production of remodeling factors associated with expression and distribution of Cx43 in the atrium.

Adipose-Derived Mesenchymal Stem Cell Transplantation in Chemotherapy-Induced Premature Ovarian Insufficiency: the Role of Connexin and Pannexin

In women undergoing chemotherapy, it is inevitable that infertility risk will increase because of impaired reproductive functions. Premature ovarian insufficiency (POI), which occurs as a devastating result of chemotherapy, is the complete depletion or dysfunction of ovarian follicles. Adipose-derived mesenchymal stem cells (ADMSCs) transplantation is among the alternative treatment methods for POI, which currently do not have an effective treatment method. Apoptosis of granulosa cells in POI is seen as the main mechanism of the disease. It is also reported that in addition to molecules directly associated with apoptosis, connexins, and pannexins are also potential effector molecules in apoptosis. The roles of these molecules in POI, which are known to play a role in many important mechanisms in the ovary, are unknown. In this study, it was aimed to analyze the expressions of Connexin43 and Pannexin1, which are thought to be effective in the formation of POI, and to show the relationship between the antiapoptotic effects of ADMSCs transplantation and these molecules in POI. For this purpose, Caspase3, Connexin43, Pannexin1 proteins, and mRNA expressions were analyzed by immunohistochemistry and RT-qPCR, and AMH levels were measured by ELISA. It was determined that Pannexin1, Caspase3 proteins, and mRNA levels increased in the POI, while Pannexin1 and Caspase3 expressions decreased in the ADMSCs treated group. While Connexin43 level decreased in POI, Connexin43 protein and mRNA levels increased in ADMSCs group. Consequently, this study demonstrated for the first time that Connexin43 and Pannexin1 were associated with apoptosis in POI. In addition, it was revealed that ADMSCs transplantation could produce antiapoptotic effects by modulating these molecules.

The Role of Connexin in Cutaneous Adverse Drug Reactions (CADRs) in Patients with Increasing Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)

Background: The occurrence of Cutaneous Adverse Drug Reactions (CADRs) is relatively rare but can be fatal when causing organ failure, especially in the liver. The supporting examinations to determine liver injury are aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Connexin-32 (Cx32) and connexin-43 (Cx43) are gap junction proteins that can be found in the liver and allegedly have a role in the mechanism of liver injury. To date, correlations between the level of connexin and aminotransferases enzyme in humans with CADRs cases are still unclear. Purpose: To determine the correlations between Cx32/Cx43 and AST/ALT levels in CADRs cases. Methods: This was a retrospective study, data collected from inpatient and outpatient’s medical records, Department of Dermatology and Venereology of Dr. Sardjito Hospital, from 2011–2015. Result: A total of 25 patients with CADRs and 35 healthy controls were included in this study. The levels between Cx32 and AST, Cx32 and ALT, Cx43 and AST, and Cx43 and ALT were not significantly correlated in CADRs cases (p>0.05). Both Cx32 and Cx43 were not significantly different between patients with and without CADRs (p>0.05). Confounding factors such as gender were not associated with this study (p>0.05). Conclusion: There was no correlation between levels of Cx32/Cx43 and increasing AST/ALT in CADRs cases. Therefore, further study is necessary to conclude the correlation between connexin and aminotransferase enzyme in CADRs patients.

Role of connexins in neurodegenerative diseases (Review).

Neurodegenerative diseases are neurological disorders characterized by progressive neuronal degeneration, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and Huntington's disease. The neuronal damage caused by these diseases may be associated with abnormal alterations of connexins in glia. These changes may cause glia to lose their ability to support and protect neurons and induce abnormal increases in levels of ions and metabolites, such as calcium ions, glutamate and ATP, around neurons. These processes eventuallys lead to neuronal death. In the present review, the abnormal expression of connexin and its primary role in neurodegenerative diseases was investigated.

Connexins-Therapeutic Targets in Cancers.

Connexins (Cx) are members of a protein family that forms intercellular channels localised in gap junction (GJ) plaques and single transmembrane channels called hemichannels. They participate in intercellular communication or communication between the intracellular and extracellular environments. Connexins affect cell homeostasis, growth and differentiation by enabling the exchange of metabolites or by interfering with various signalling pathways. Alterations in the functionality and the expression of connexins have been linked to the occurrence of many diseases. Connexins have been already linked to cancers, cardiac and brain disorders, chronic lung and kidney conditions and wound healing processes. Connexins have been shown either to suppress cancer tumour growth or to increase tumorigenicity by promoting cancer cell growth, migration and invasiveness. A better understanding of the complexity of cancer biology related to connexins and intercellular communication could result in the design of novel therapeutic strategies. The modulation of connexin expression may be an effective therapeutic approach in some types of cancers. Therefore, one important challenge is the search for mechanisms and new drugs, selectively modulating the expression of various connexin isoforms. We performed a systematic literature search up to February 2020 in the electronic databases PubMed and EMBASE. Our search terms were as follows: connexins, hemichannels, cancer and cancer treatment. This review aims to provide information about the role of connexins and gap junctions in cancer, as well as to discuss possible therapeutic options that are currently being studied.

The Role of Connexins and Pannexins in the Cell Communications of Bone Cells

Connexins and Pannexins play important roles in osteocytes and osteoblasts differentiation, intracellular signal transduction, maintenance of bone balance, and bone regeneration. This article reviews the progress and limitations of Connexins-mediated gap junctions and Pannexins mediated hemichannel in bone. Current research has shown that these molecules, in the form of gap junctions or separate hemichannels, deliver external stimuli to the skeletal system. However, little is known about the role of other cell types in bone development and homeostasis, such as pre-osteoblasts and bone marrow mesenchymal stem cells, in maintaining normality. In addition, at present, the most well-studied member of the Connexins family is Connexin43 (Cx43), while the roles and mechanisms of other members in bone development are still behind the veil. Gene-edited animal models provide basic information on the role of Connexins and Pannexins in the skeletal system, but the similarities and differences between Connexins and Pannexins remain to be discovered. Targeting a specific function of Connexins or Pannexins for bone stimulation and bone disease remains a challenge, with pharmacological selective overlap between channels, compensation of other subtypes, differences in methods for assessing channel function, and genetic changes associated with transgenic mouse models. Therefore, better tools and research pathways are needed to understand the role of these pathways in bone and cartilage. An essential task for future research will be to identify specific compounds that regulate Connexins or Pannexins subtypes to enable them to be used as pharmaceutical agents in the treatment of bone diseases, providing the possibility to develop new therapeutic strategies for improving bone health and treating diseases of the skeletal system.

Consideration of Pannexin 1 channels in COVID-19 pathology and treatment.

Pannexin1 (PANX1) is a ubiquitously expressed, channel-forming protein found in a number of tissues thoughout the body (e.g. lung, vasculature, liver, central nervous system, immune system) that is important in many key physiological and immune responses. PANX1 channels passively flux ATP (predominantly), multiple metabolites, and likely other small anions. PANX1 channels regulate inflammation and host responses to several pathogens, including viruses. While there is currently no evidence suggesting novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and PANX1 directly interact, there is an urgent need for therapeutic strategies, especially those targeting the hyper-inflammation and cytokine storm that occurs in severe cases of COVID-19. Here we argue that PANX1, and drugs known to target PANX1 (including the FDA-approved drug probenecid), should be the focus of further investigation in the context of SARS-CoV-2 infection and its associated pathology in COVID-19 patients.

The important role of connexin 43 in subarachnoid hemorrhage-induced cerebral vasospasm

BackgroundGap junctions are involved in the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). However, the specific roles and regulatory functions of related connexin isoforms remain unknown. The aim of this study was to investigate the importance of connexin 43 (Cx43) in CVS and determine whether Cx43 alterations are modulated via the protein kinase C (PKC) signaling transduction pathway.MethodsOxyhemoglobin (OxyHb)-induced smooth muscle cells of basilar arterial and second-injection model in rat were used as CVS models in vitro and in vivo. In addition, dye transfer assays were used for gap junction-mediated intercellular communication (GJIC) observation in vitro and delayed cerebral ischemia (DCI) was observed in vivo by perfusion-weighted imaging (PWI) and intravital fluorescence microscopy.ResultsIncrease in Cx43 mediated the development of SAH-induced CVS was found in both in vitro and in vivo CVS models. Enhanced GJIC was observed in vitro CVS model, this effect and increased Cx43 were reversed by preincubation with specific PKC inhibitors (chelerythrine or GF 109203X). DCI was observed in vivo on day 7 after SAH. However, DCI was attenuated by pretreatment with Cx43 siRNA or PKC inhibitors, and the increased Cx43 expression in vivo was also reversed by Cx43 siRNA or PKC inhibitors.ConclusionsThese data provide strong evidence that Cx43 plays an important role in CVS and indicate that changes in Cx43 expression may be mediated by the PKC pathway. The current findings suggest that Cx43 and the PKC pathway are novel targets for developing treatments for SAH-induced CVS.

Connexin 50 and AQP0 are Essential in Maintaining Organization and Integrity of Lens Fibers.

PurposeConnexins and aquaporins play essential roles in maintaining lens homeostasis and transparency and there is a close physical and functional relationship between these two proteins. Aquaporin 0 (AQP0), in addition to its role in water transport in the lens, acts as a cell–cell adhesion molecule. Recently, we showed a new role of connexin (Cx) 50 in mediating cell–cell adhesion. However, the cooperative roles of these two proteins in the lens in vivo have not been reported.MethodsWe generated an AQP0/Cx50 double knockout (dKO) mouse model. Light, fluorescence, transmission thin section, and freeze-fracture electron microscopy, as well as wheat germ agglutinin and phalloidin labeling were used to evaluate lens structure. Mechanical properties of lenses were determined by mechanical compression testing.ResultsDKO mice exhibited small eyes and lenses with severe cataracts, along with lens posterior defects, including posterior capsule rupture. The dKO mouse lenses had severe structural disruption associated with increased spaces between lens fiber cells when compared with wild-type lenses or lenses deficient in either Cx50 or AQP0. DKO mice also exhibited greater reduction in lens size compared with Cx50 KO mice. Gap-junction plaque size was greatly decreased in cortical fiber cells in dKO mice. Moreover, lens stiffness and elasticity were completely diminished, exhibiting a gelatinous texture in adult dKO mice.ConclusionsThis novel mouse model reveals that Cx50 and AQP0 play an important role in mediating cell–cell adhesion function in the lens fiber cells and their deficiency impairs lens fiber organization, integrity, mechanical properties, and lens development.

Progress in research on connexins in diabetic retinopathy

Diabetic retinopathy is the most common microvascular complication of diabetes. It is one of the major blinding diseases in the world. The intercellular communication function of connexins plays a key role in maintaining retinal microvascular homeostasis. The connexins involve in the development of diabetic retinopathy. This article reviews the role of connexins in the pathogenesis of diabetic retinopathy. Key words: Connexin; Gap junction intercellular communication; Diabetic retinopathy

Role of Connexins in Chronic Pain and Their Potential as Therapeutic Targets for Next-Generation Analgesics

Chronic pain, including inflammatory, neuropathic pain, is a serious clinical issue. There are increasing numbers of patients with chronic pain due to the growing number of elderly and it is estimated that about 25% of the global population will develop chronic pain. Chronic pain patients are refractory to medications used to treat acute pain such as opioids and non-steroidal anti-inflammatory drugs. Furthermore, the complexity and diversity of chronic pain mechanisms hinder the development of new analgesics. Thus, a better understanding of the mechanism of chronic pain is needed, which would facilitate the development of novel analgesics based on novel mechanisms. With this goal, connexins (Cxs) could be targeted for the development of new analgesics. Connexins are proteins with 20 subtypes, and function as channels, gap junctions between cells, and hemichannels that sample the extracellular space and release molecules such as neurotransmitters. Furthermore, Cxs could have functions independent of channel activity. Recent studies have shown that Cxs could be crucial in the induction and maintenance of chronic pain, and modulation of the activity or the expression of Cxs ameliorates nociceptive hypersensitivity in multiple chronic pain models. This review will cite novel findings on the role of of Cxs in the nociceptive transduction pathway under the chronic pain state and antinociceptive effects of various molecules modulating activity or expression of Cxs. Also, the potential of Cx modulation as a therapeutic strategy for intractable chronic pain will be discussed.

The role and therapeutic potential of connexins, pannexins and their channels in Parkinson's disease

Lack of effective medication for slowing down progression of Parkinson's disease (PD) as a highly prevalent neurodegenerative disorder requires novel avenues of scientific investigation to elucidate the underlying molecular and cellular mechanisms. Studying connexins, pannexins and their channels has uncovered their potential role in mediating communication and signaling pathways that drive neurodegenerative diseases, including PD. Indeed, given their critical role in tissue homeostasis, it is not surprising that connexins, pannexins and their channels are frequently involved in pathological processes. For this reason, pharmacological tools to further clarify their functions and to validate connexins, pannexins and their channels as drug targets for the development of novel therapies for PD treatment are urgently needed. In this paper, a state-of-the-art overview is provided of current neuropathological and molecular understanding of PD. Focus is put on the roles of connexins, pannexins and their channels, in particular in the development of potential innovative disease-modifying therapies for PD treatment.

The Role of Connexin and Pannexin Channels in Perinatal Brain Injury and Inflammation.

Perinatal brain injury remains a major cause of death and life-long disability. Perinatal brain injury is typically associated with hypoxia-ischemia and/or infection/inflammation. Both hypoxia-ischemia and infection trigger an inflammatory response in the brain. The inflammatory response can contribute to brain cell loss and chronic neuroinflammation leading to neurological impairments. It is now well-established that brain injury evolves over time, and shows a striking spread from injured to previously uninjured regions of the brain. There is increasing evidence that this spread is related to opening of connexin hemichannels and pannexin channels, both of which are large conductance membrane channels found in almost all cell types in the brain. Blocking connexin hemichannels within the first 3 h after hypoxia-ischemia has been shown to improve outcomes in term equivalent fetal sheep but it is important to also understand the downstream pathways linking membrane channel opening with the development of injury in order to identify new therapeutic targets. Open membrane channels release adenosine triphosphate (ATP), and other neuroactive molecules, into the extracellular space. ATP has an important physiological role, but has also been reported to act as a damage-associated molecular pattern (DAMP) signal mediated through specific purinergic receptors and so act as a primary signal 1 in the innate immune system inflammasome pathway. More crucially, extracellular ATP is a key inflammasome signal 2 activator, with purinergic receptor binding triggering the assembly of the multi-protein inflammasome complex. The inflammasome pathway and complex formation contribute to activation of inflammatory caspases, and the release of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-18, and vascular endothelial growth factor (VEGF). We propose that the NOD-like receptor protein-3 (NLRP3) inflammasome, which has been linked to inflammatory responses in models of ischemic stroke and various inflammatory diseases, may be one mechanism by which connexin hemichannel opening especially mediates perinatal brain injury.

Role of connexin 40 in male predisposition to atrial fibrillation

Role of connexin 40 in male predisposition to atrial fibrillation

Connexins and Atrial Fibrillation in Obstructive Sleep Apnea.

To summarize the potential interactions between obstructive sleep apnea (OSA), atrial fibrillation (AF), and connexins. OSA is highly prevalent in patients with cardiovascular disease, and is associated with increased risk for end-organ substantial morbidities linked to autonomic nervous system imbalance, increased oxidative stress and inflammation, ultimately leading to reduced life expectancy. Epidemiological studies indicate that OSA is associated with increased incidence and progression of coronary heart disease, heart failure, stroke, as well as arrhythmias, particularly AF. Conversely, AF is very common among subjects referred for suspected OSA, and the prevalence of AF increases with OSA severity. The interrelationships between AF and OSA along with the well-known epidemiological links between these two conditions and obesity may reflect shared pathophysiological pathways, which may depend on the intercellular diffusion of signaling molecules into either the extracellular space or require cell-to-cell contact. Connexin signaling is accomplished via direct exchanges of cytosolic molecules between adjacent cells at gap membrane junctions for cell-to-cell coupling. The role of connexins in AF is now quite well established, but the impact of OSA on cardiac connexins has only recently begun to be investigated. Understanding the biology and regulatory mechanisms of connexins in OSA at the transcriptional, translational, and post-translational levels will undoubtedly require major efforts to decipher the breadth and complexity of connexin functions in OSA-induced AF. The risk of end-organ morbidities has initiated the search for circulating mechanistic biomarker signatures and the implementation of biomarker-based algorithms for precision-based diagnosis and risk assessment. Here we summarize recent findings in OSA as they relate to AF risk, and also review potential mechanisms linking OSA, AF and connexins.