Ask about this productRelated genes to: GJA9 antibody
- Gene:
- GJA9 NIH gene
- Name:
- gap junction protein alpha 9
- Previous symbol:
- GJA10
- Synonyms:
- CX59, CX58
- Chromosome:
- 1p34.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-09-05
- Date modifiied:
- 2016-10-05
- Gene:
- GJD2 NIH gene
- Name:
- gap junction protein delta 2
- Previous symbol:
- GJA9
- Synonyms:
- CX36
- Chromosome:
- 15q14
- Locus Type:
- gene with protein product
- Date approved:
- 2007-01-16
- Date modifiied:
- 2016-10-05
Related products to: GJA9 antibody
Related articles to: GJA9 antibody
- Within the islets of Langerhans, gap junction coupling is important for synchronizing oscillatory free-calcium activity ([Ca2+]) and regulating pulsatile insulin release. In islets from multiple models of diabetes, gap junction coupling is disrupted, and [Ca2+] synchronization and pulsatile insulin is lost. Functional subpopulations have been identified within the islet that are linked to driving synchronized [Ca2+] and insulin release. These subpopulations can be disrupted under conditions associated with diabetes, such as glucolipotoxicity and inflammatory environments, and their loss may drive islet dysfunction. Here we investigated how loss of gap junction coupling influences functional subpopulations under diabetogenic environments. We treated islets with a cocktail of pro-inflammatory cytokines and protected gap junction coupling via co-treatment with a Cx36 peptide S293 that was previously shown to specifically prevent a decline in gap junction permeability and synchronized [Ca2+] dynamics. We performed calcium imaging and ChR2 stimulation and analyzed islet [Ca2+] dynamics and the presence of functional subpopulations, including hubs and first-responders. 1- or 24-h cytokine treatment disrupted gap junction coupling, which was fully prevented by S293 peptide co-treatment. Treatment with pro-inflammatory cytokines decreased the recruitment of [Ca2+] upon ChR2 stimulation, increased the time between first and last responding cells upon glucose stimulation, and reduced the number and consistency of hub cells. When preserving gap junction coupling by S293 during cytokine treatment, the presence and consistency of these subpopulations were only marginally improved. We therefore concluded that while gap junction coupling is important for functional subpopulations to exert their influence on islet function, the restoration of gap junctions alone is not sufficient to recover functional subpopulations under diabetogenic conditions. Thus, preventing a disruption to intrinsic β-cell properties that define functional subpopulations is likely important for preserving these subpopulations during diabetes. - Source: PubMed
Publication date: 2026/03/31
Levitt Claire HIsaacs DominicHansen Maria SKravets ViraBriggs Jennifer KBenninger Richard K P - Connexin36 (Cx36) is highly expressed in inhibitory and excitatory neurons as well as pancreatic β-cells, where it forms gap junction channels that coordinate metabolic and electrical responses. In addition, Cx36 forms hemichannels in pancreatic β-cells, where it may play a critical role in endocrine cell signaling. Despite this, the regulatory mechanisms and biophysical properties of Cx36 HCs remain poorly understood. Using HeLa cells lacking endogenous expression of large-pore channels and transfected with mouse Cx36-EGFP, we evaluated hemichannel activity through dye uptake assays and membrane current recordings. We found that Cx36 hemichannel activity is strongly inhibited by extracellular Mg, rather than Ca, in contrast to hemichannels formed by other connexins. Under reduced extracellular Mg, or under alkaline extracellular pH conditions, Cx36 hemichannels exhibited increased activity and allowed Ca influx, as detected by ratiometric dye FURA-2. Under low extracellular Mg conditions, Cx36 hemichannels exhibited increased permeability to small molecules and were blocked by La and quinine, but not by high glucose concentration. In-silico studies revealed interactions between Mg and two amino acid residues within a pore constriction (D47-E49), which alter the electrostatic potential of the hemichannel pore. Consistent with these observations, mutation of either amino acid residue to alanine (D47A or E49A) markedly reduced the inhibitory effect of extracellular Mg. Together, these findings offer critical insights into the regulation of Cx36 hemichannels and suggest that alterations in Mg homeostasis may have significant consequences for Cx36-mediated signaling. - Source: PubMed
Publication date: 2026/03/16
García AníbalMárquez-Miranda ValeriaBravo-Acuña NicolásAraya-Duran IngridRojas MaximilianoPalacios-Prado NicolásO'Brien JohnGonzález-Nilo Fernando DSáez Juan C - The output mitral cells (MCs) and tufted cells (TCs) of the mammalian olfactory bulb (OB) are coupled through both chemical mechanisms as well as gap junctions that are mediated by connexin 36 (Cx36). Here, we tested both behavioural and physiological effects of eliminating gap junctions in knockout (KO) mice with homozygous deletions of Cx36. In a go/no-go associative learning task, Cx36 KO mice were found to display reduced discrimination capabilities when presented with pairs of stimuli that included a monomolecular odour and mixtures that had the same monomolecular odour and a small amount of a structurally similar odour. The impairments did not occur for less similar odour pairs, suggesting that Cx36 KO mice have olfactory processing deficits that are specific to fine odour discrimination. In physiological recordings in OB slices from Cx36 KO mice, MCs displayed reduced excitation in response to electrical stimulation of sensory afferents, both single stimulus pulses as well as a theta burst pattern designed to mimic sniffing. The reduction in MC excitatory current was most prominent for late portions of their response, 300 ms after single stimulus pulses or following all theta bursts that came after the first. More global local field potentials recorded in OB glomeruli were largely unaffected by Cx36 KO. We suggest that the KO-induced impairments in fine odour discrimination could be linked to reduced late-phase MC excitation because of the longer time that mice require to make difficult odour discriminations. KEY POINTS: The output mitral cells (MCs) of the olfactory bulb (OB) engage in strong electrical coupling via connexin 36 (Cx36)-mediated gap junctions. However, the behavioural and physiological relevance of these gap junctions is not well understood. In studies conducted in Cx36 knockout (KO) mice, we found impaired odour discrimination vs. wild-type mice in a go/no-go associative learning task, although deficits only occurred with the most difficult tasks involving odour mixtures. These results provide the first evidence to date of olfactory behavioural deficits in Cx36 KO mice. In OB slices, Cx36 KO reduced excitatory responses in MCs to electrical stimulation of sensory afferents, but only during latter stages of the response. We suggest that KO-induced impairments in fine odour discrimination could be linked to reduced late-phase MC excitation because of the longer time that mice require to make difficult odour discriminations. - Source: PubMed
Publication date: 2025/12/10
Kuruppath PraveenJones Shelly TPouille FredericRamirez-Gordillo DanielRestrepo DiegoSchoppa Nathan E - In this review we propose the hypothesis that an energy-dissipating process precedes the continuous stimulation of insulin secretion by glucose. This process is mediated by connexin 36 hemichannels (Cx36H), or Cx36 connexons. Cx36H oligomers are expressed at the plasma membrane, and their gating activity (opening) is activated by plasma membrane depolarization after the closure of KATP channels by glucose (>5 mM) metabolism. This initial depolarization (1st step) might be responsible for the first phase of insulin secretion, with the subsequent opening of Cx36H increasing β-cell plasma membrane permeability, allowing for the efflux of metabolites (less than 1KD) (GABA, adenine nucleotides) and K (2nd step). This provokes a breakdown of oxidative glucose metabolism and the repolarization of the plasma membrane. As the extracellular glucose concentration increases further (>>5 mM), it exerts a progressive inhibition effect on Cx36H opening, allowing for the continuous stimulation of insulin secretion (3d step, second phase,). The glucose feature of regulating Cx36H closing with sigmoidal kinetics (8 mM IC and around 20 mM at maximum) has been confirmed in mouse Cx36 connexin expression in Xenopus oocytes and in mouse islets stimulated by a range of glucose concentrations in the presence of 70 mM KCl. This gating activity was also inhibited by some non-metabolized glucose analogs. Glucose inhibition of Cx3H opening might not only contribute to making the insulin secretory response more specific for glucose but might also play a role in the pulsatility of sustained insulin secretion. Cx36H opening also offers the opportunity to potentiate the secretory effect in vivo by, permeant or not, metabolic stimuli. Confirmation of this novel physiological role for Cx36H in β-cells would place them as new susceptibility locus for type 1 and type 2 diabetes, whose physiological implication in the mechanism of insulin secretion regulation should be evaluated by in vivo studies in diabetic patients. - Source: PubMed
Publication date: 2025/10/22
Tamarit-Rodriguez Jorge - A corneal alkali burn can cause irreversible damage to both the cornea and retina. This study aims to investigate the role of the gap junction subunit connexin 36 (Cx36) in mediating secondary cell death and its impact on the apoptosis of retinal ganglion cells (RGCs) following ocular alkali burns, contributing to irreversible vision loss. - Source: PubMed
Qiu ChunTingZhang TingWang QinYang KangyiSo ChunghimPan Feng