Gap junction is the aggregate of some intercellular channels, which allows ions and small molecules to transport or transfer between cells. There are about 20 proposed members of the connexin family found in mammalian tissues now, and more than 10 reported are expressed in the nervous system. The astrocytes and oligodendrocytes express some specific connexins. In the present article, we review the recent literatures to illustrate the importance of gap junction for the intercellular communication between glial cells, astrocytes and neurons, and neuronal cells, which is crucial for brain functions.
Brain ; metabolism ; physiology ; Connexins ; metabolism ; Gap Junctions ; metabolism ; physiology ; Humans ; Neuroglia ; metabolism ; physiology ; Neurons ; metabolism ; physiology

OBJECTIVEThis review discusses the experimental and clinical studies those show the expression of connexin 36 in the central nervous system and the possible role of connexin 36 in epileptic seizure.

DATA SOURCESAll articles used in this review were mainly searched from PubMed published in English from 1996 to 2012.

STUDY SELECTIONOriginal articles and reviews were selected if they were related to the expression of connexin 36 in the central nervous system and its role in epilepsy.

RESULTSThe distribution of connexin 36 is developmentally regulated, cell-specific and region-specific. Connexin 36 is involved in some neuronal functions and epileptic synchronization. Changes in the connexin 36 gene and protein were accompanied by seizures. Selective gap junction blockers have exerted anticonvulsant actions in a variety of experiments examined in both humans and experimental animals.

CONCLUSIONSConnexin 36 plays an important role in both physiological and pathological conditions in the central nervous system. A better understanding of the role of connexin 36 in seizure activity may contribute to the development of new therapeutic approaches to treating epilepsy.

Animals ; Central Nervous System ; metabolism ; Connexins ; metabolism ; Gap Junctions ; metabolism ; Humans ; Seizures ; metabolism

Objective To study the effect of overwork stress response on the expression of connexin 43（Cx43） and connexin 45（Cx45） in cardiomyocytes and on cardiac function. Methods The experimental animals were divided into control group, overworked 1-month group and overworked 2-month group. A overworked rat model was established by forcing swimming of overworked group. The expressions of Cx43 and Cx45 in myocardial tissues of experimental animals were detected by Western blotting, while the corresponding myocardial tissues were stained with hematoxylin-eosin （HE） staining and Masson's staining, then histologically observed. Results Western blotting results showed that, compared with the control group, Cx43 expression in myocardial tissues of overworked rats decreased while Cx45 expression increased. HE staining and Masson's staining results showed that hypertrophy, rupture and interstitial fiber tissue hyperplasia were observed in myocardial fibers of overworked rats. Conclusion Overwork stress response may affect cardiac function as an independent factor and may even cause heart failure or arrhythmias and lead to death.
Animals ; Arrhythmias, Cardiac/metabolism* ; Connexin 43/metabolism* ; Connexins/metabolism* ; Heart Failure ; Myocardium ; Myocytes, Cardiac/metabolism* ; Rats

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Creatine/metabolism* ; Extracellular Vesicles ; Muscle, Skeletal/metabolism* ; Myoblasts/metabolism* ; Regeneration ; Connexins/metabolism*

OBJECTIVETo probe into expression of connexin 43 (Cx43) in the meridians of the normal healthy rats and the relation among connexin, gap junction and meridian.

METHODSPowerVision two step immunohistochemical technique and ASIAS-2000 automatical image-scan analyzing system were used to detect Cx43 level and distribution in the Kidney and Bladder Meridians of the rat.

RESULTSCx43 expressed mainly in skin epithelia, fibroblasts and mast cells of the subcutaneous layer. And expression of Cx43 in the Kidney and Bladder Meridians was significantly more than that in the control lines (P < 0.01).

CONCLUSIONConnexins and gap junctions have close relation with the meridians, and the gap junctional intercellular communication may play an important role in the function of meridians.

Animals ; Cell Communication ; Connexin 43 ; metabolism ; Connexins ; Gap Junctions ; metabolism ; Meridians ; Rats

Gap junctions play a critical role in electrical synchronization and exchange of small molecules between neighboring cells; connexins are a family of structurally related transmembrane proteins that assemble to form vertebrate gap junctions. Hyperglycemia changes the structure gap junction proteins and their expression, resulting in obstruction of neural regeneration, vascular function and wound healing, and also promoting vascular atherosclerosis. These pathogenic factors would cause diabetic foot ulcers. This article reviews the involvement of connexins in pathogenesis of diabetic foot.
Atherosclerosis ; Connexins ; metabolism ; Diabetic Foot ; pathology ; Gap Junctions ; metabolism ; Humans ; Hyperglycemia ; physiopathology ; Regeneration ; Wound Healing

OBJECTIVETo investigate the expressions of Cx26, Cx32 and Cx43 in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their roles in the development and progression of PCa in order to provide some novel evidence for the diagnosis and treatment of PCa.

METHODSWe determined the expressions of Cx26, Cx32 and Cx43 in the paraffin samples from 31 cases of PCa and 23 cases of BPH by SABC immunohistochemical staining, and analyzed the relationship of their expressions with the clinical and pathological parameters of PCa and BPH using the semiquantitative method.

RESULTSThe positive expressions of Cx26 in BPH and PCa were 82.6% and 74.2%, respectively (chi2 = 0.541, P > 0.05), those of Cx32 were 78.3% and 61.3% (chi2 = 1.763, P > 0.05), and those of Cx43 were 87.0% and 38.7% (chi2 = 12.730, P < 0.01). The staining intensities of Cx26 and Cx43 were negatively correlated with the malignant phenotype of PCa (rCx26 = -0.476, P < 0.01; rCx43 = -0.484, P < 0.01), but not the expression of Cx32 (r = -0.242, P > 0.05). The three Cxs exhibited no correlation with the age and serum PSA level of the patients (P > 0.05), nor among their expressions (P > 0.05).

CONCLUSIONCx26, Cx32 and Cx43 are expressed in different degrees in BPH and PCa tissues. Cx43 plays a role in the occurrence and progression of PCa, and may serve as a new marker of PCa besides PSA as well as a new target in the biotherapy of PCa. Cx26 may be partially involved in the progression of PCa, but its mechanisms need to be further studied.

Aged ; Aged, 80 and over ; Connexin 26 ; Connexin 43 ; metabolism ; Connexins ; metabolism ; Humans ; Male ; Prostate ; metabolism ; Prostatic Neoplasms ; metabolism

Voltage is an important parameter that regulates the conductance of both intercellular and plasma membrane channels (undocked hemichannels) formed by the 21 members of the mammalian connexin gene family. Connexin channels display two forms of voltage-dependence, rectification of ionic currents and voltage-dependent gating. Ionic rectification results either from asymmetries in the distribution of fixed charges due to heterotypic pairing of different hemichannels, or by channel block, arising from differences in the concentrations of divalent cations on opposite sides of the junctional plaque. This rectification likely underpins the electrical rectification observed in some electrical synapses. Both intercellular and undocked hemichannels also display two distinct forms of voltage-dependent gating, termed Vj (fast)-gating and loop (slow)-gating. This review summarizes our current understanding of the molecular determinants and mechanisms underlying these conformational changes derived from experimental, molecular-genetic, structural, and computational approaches.
Animals ; Connexins/chemistry/*metabolism ; Humans ; *Ion Channel Gating ; Ion Channels/chemistry/*metabolism ; Molecular Dynamics Simulation ; Protein Conformation

Homoeostasis depends on the close connection and intimate molecular exchange between extracellular, intracellular and intercellular networks. Intercellular communication is largely mediated by gap junctions (GJs), a type of specialized membrane contact composed of variable number of channels that enable direct communication between cells by allowing small molecules to pass directly into the cytoplasm of neighbouring cells. Although considerable evidence indicates that gap junctions contribute to the functions of many organs, such as the bone, intestine, kidney, heart, brain and nerve, less is known about their role in oral development and disease. In this review, the current progress in understanding the background of connexins and the functions of gap junctions in oral development and diseases is discussed. The homoeostasis of tooth and periodontal tissues, normal tooth and maxillofacial development, saliva secretion and the integrity of the oral mucosa depend on the proper function of gap junctions. Knowledge of this pattern of cell-cell communication is required for a better understanding of oral diseases. With the ever-increasing understanding of connexins in oral diseases, therapeutic strategies could be developed to target these membrane channels in various oral diseases and maxillofacial dysplasia.
Bone and Bones ; Cell Communication ; Connexins ; metabolism ; physiology ; Gap Junctions ; metabolism ; pathology ; Homeostasis ; physiology ; Humans ; Mouth Diseases ; Phosphorylation

Gap junctions construct hydrophilic trans-membrane channels which adjust the intercellular communication of chemistry and electricity. In the heart, individual cardiac myocytes are linked by gap junctions. These junctions form low resistance pathways along which the electrical impulse flows rapidly and repeatedly between all the myocardium, ensuring their synchronous contraction. In recent years, some researchers have found that connexins, the protein molecules of gap junction channels, are reduced in number or redistributed from intercalated disks (ID) to lateral cell borders in a variety of cardiac disease, especially in ischemic heart disease. The gap junction remodeling is considered to be arrhythmogenic. These findings will lead us to a new realm in the diagnostic of sudden death caused by coronary heart disease.
Animals ; Cell Communication/physiology* ; Connexins/metabolism* ; Coronary Disease/complications* ; Death, Sudden/etiology* ; Gap Junctions/metabolism* ; Humans ; Immunohistochemistry ; Myocardium/pathology*