{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:01:53Z","timestamp":1788778913055,"version":"build-2803163510"},"reference-count":170,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T00:00:00Z","timestamp":1718409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Padua","award":["BORT_BIRD23_01"],"award-info":[{"award-number":["BORT_BIRD23_01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Connexin hemichannels (HCs) expressed at the plasma membrane of mammalian cells are of paramount importance for intercellular communication. In physiological conditions, HCs can form gap junction (GJ) channels, providing a direct diffusive path between neighbouring cells. In addition, unpaired HCs provide conduits for the exchange of solutes between the cytoplasm and the extracellular milieu, including messenger molecules involved in paracrine signalling. The synergistic action of membrane potential and Ca2+ ions controls the gating of the large and relatively unselective pore of connexin HCs. The four orders of magnitude difference in gating sensitivity to the extracellular ([Ca2+]e) and the cytosolic ([Ca2+]c) Ca2+ concentrations suggests that at least two different Ca2+ sensors may exist. While [Ca2+]e acts as a spatial modulator of the HC opening, which is most likely dependent on the cell layer, compartment, and organ, [Ca2+]c triggers HC opening and the release of extracellular bursts of messenger molecules. Such molecules include ATP, cAMP, glutamate, NAD+, glutathione, D-serine, and prostaglandins. Lost or abnormal HC regulation by Ca2+ has been associated with several diseases, including deafness, keratitis ichthyosis, palmoplantar keratoderma, Charcot\u2013Marie\u2013Tooth neuropathy, oculodentodigital dysplasia, and congenital cataracts. The fact that both an increased and a decreased Ca2+ sensitivity has been linked to pathological conditions suggests that Ca2+ in healthy cells finely tunes the normal HC function. Overall, further investigation is needed to clarify the structural and chemical modifications of connexin HCs during [Ca2+]e and [Ca2+]c variations. A molecular model that accounts for changes in both Ca2+ and the transmembrane voltage will undoubtedly enhance our interpretation of the experimental results and pave the way for developing therapeutic compounds targeting specific HC dysfunctions.<\/jats:p>","DOI":"10.3390\/ijms25126594","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T11:14:16Z","timestamp":1718622856000},"page":"6594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Calcium Regulation of Connexin Hemichannels"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9660-5535","authenticated-orcid":false,"given":"Erva","family":"Bayraktar","sequence":"first","affiliation":[{"name":"Veneto Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padova, Italy"},{"name":"Department of Physics and Astronomy \u201cG. Galilei\u201d, University of Padua, Via Marzolo 8, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6178-5951","authenticated-orcid":false,"given":"Diego","family":"Lopez-Pigozzi","sequence":"additional","affiliation":[{"name":"Veneto Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padova, Italy"},{"name":"Department of Physics and Astronomy \u201cG. Galilei\u201d, University of Padua, Via Marzolo 8, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7198-9838","authenticated-orcid":false,"given":"Mario","family":"Bortolozzi","sequence":"additional","affiliation":[{"name":"Veneto Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padova, Italy"},{"name":"Department of Physics and Astronomy \u201cG. Galilei\u201d, University of Padua, Via Marzolo 8, 35131 Padova, Italy"},{"name":"Institute of Endocrinology and Oncology \u201cGaetano Salvatore\u201d (IEOS-CNR), Via Pietro Castellino 111, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Delmar, M., Laird, D.W., Naus, C.C., Nielsen, M.S., Verselis, V.K., and White, T.W. (2018). Connexins and Disease. Cold Spring Harb. Perspect. Biol., 10.","DOI":"10.1101\/cshperspect.a029348"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bbamem.2017.05.018","article-title":"Intracellular trafficking pathways of Cx43 gap junction channels","volume":"1860","author":"Epifantseva","year":"2018","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4475","DOI":"10.1073\/pnas.0511118103","article-title":"S-nitrosylation and permeation through connexin 43 hemichannels in astrocytes: Induction by oxidant stress and reversal by reducing agents","volume":"103","author":"Retamal","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"C665","DOI":"10.1152\/ajpcell.00200.2009","article-title":"Metabolic inhibition increases activity of connexin-32 hemichannels permeable to Ca2+ in transfected HeLa cells","volume":"297","author":"Sanchez","year":"2009","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1017\/S0033583501003705","article-title":"Emerging issues of connexin channels: Biophysics fills the gap","volume":"34","author":"Harris","year":"2001","journal-title":"Q. Rev. Biophys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.2174\/0929867033456927","article-title":"Transfer of biologically important molecules between cells through gap junction channels","volume":"10","author":"Alexander","year":"2003","journal-title":"Curr. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1016\/j.yexcr.2010.05.026","article-title":"Cell membrane permeabilization via connexin hemichannels in living and dying cells","volume":"316","author":"Saez","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18770","DOI":"10.1073\/pnas.0800793105","article-title":"ATP release through connexin hemichannels and gap junction transfer of second messengers propagate Ca2+ signals across the inner ear","volume":"105","author":"Anselmi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/ncb1021","article-title":"Connexin-dependent inter-cellular communication increases invasion and dissemination of Shigella in epithelial cells","volume":"5","author":"Clair","year":"2003","journal-title":"Nat. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s11302-010-9192-9","article-title":"ATP-mediated cell\u2013cell signaling in the organ of Corti: The role of connexin channels","volume":"6","author":"Majumder","year":"2010","journal-title":"Purinergic Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1681\/ASN.2008101099","article-title":"Connexin 30 deficiency impairs renal tubular ATP release and pressure natriuresis","volume":"20","author":"Sipos","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s12013-011-9188-2","article-title":"Human connexin30.2\/31.3 (GJC3) does not form functional gap junction channels but causes enhanced ATP release in HeLa cells","volume":"61","author":"Liang","year":"2011","journal-title":"Cell Biochem. Biophys."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/sj.emboj.7600908","article-title":"Intracellular calcium changes trigger connexin 32 hemichannel opening","volume":"25","author":"Decrock","year":"2006","journal-title":"EMBO J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.bbrc.2008.01.054","article-title":"ATP release by way of connexin 36 hemichannels mediates ischemic tolerance in vitro","volume":"368","author":"Schock","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/jcp.20440","article-title":"Endogenous hemichannels play a role in the release of ATP from Xenopus oocytes","volume":"206","author":"Bahima","year":"2006","journal-title":"J. Cell. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R1769","DOI":"10.1152\/ajpregu.00489.2007","article-title":"Connexin 40 and ATP-dependent intercellular calcium wave in renal glomerular endothelial cells","volume":"294","author":"Toma","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15735","DOI":"10.1073\/pnas.95.26.15735","article-title":"Connexins regulate calcium signaling by controlling ATP release","volume":"95","author":"Cotrina","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1523\/JNEUROSCI.5048-07.2008","article-title":"Connexin 43 hemichannels are permeable to ATP","volume":"28","author":"Kang","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1093\/cvr\/cvs187","article-title":"Mechanisms of ATP release and signalling in the blood vessel wall","volume":"95","author":"Lohman","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10482","DOI":"10.1074\/jbc.M109902200","article-title":"Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels","volume":"277","author":"Stout","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1167\/iovs.04-1181","article-title":"ATP release through connexin hemichannels in corneal endothelial cells","volume":"46","author":"Gomes","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1152\/physrev.00029.2011","article-title":"Intercellular Ca(2+) waves: Mechanisms and function","volume":"92","author":"Leybaert","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3389\/fphar.2013.00075","article-title":"Cyclic nucleotide permeability through unopposed connexin hemichannels","volume":"4","author":"Valiunas","year":"2013","journal-title":"Front. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3588","DOI":"10.1523\/JNEUROSCI.23-09-03588.2003","article-title":"Functional hemichannels in astrocytes: A novel mechanism of glutamate release","volume":"23","author":"Ye","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21362","DOI":"10.1074\/jbc.M600504200","article-title":"Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner","volume":"281","author":"Takeuchi","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1096\/fj.00-0566fje","article-title":"Connexin 43 hemi channels mediate Ca2+-regulated transmembrane NAD+ fluxes in intact cells","volume":"15","author":"Bruzzone","year":"2001","journal-title":"FASEB J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1096\/fj.00-0803fje","article-title":"Paracrinally stimulated expansion of early human hemopoietic progenitors by stroma-generated cyclic ADP-ribose","volume":"15","author":"Zocchi","year":"2001","journal-title":"FASEB J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.neulet.2006.12.043","article-title":"Gap junction hemichannel-mediated release of glutathione from cultured rat astrocytes","volume":"415","author":"Rana","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e22134","DOI":"10.1096\/fj.202100798RR","article-title":"Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdala","volume":"36","author":"Linsambarth","year":"2022","journal-title":"FASEB J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1091\/mbc.e04-10-0912","article-title":"Mechanical strain opens connexin 43 hemichannels in osteocytes: A novel mechanism for the release of prostaglandin","volume":"16","author":"Cherian","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"239","DOI":"10.4161\/cib.2.3.8154","article-title":"Connexin 43 hemichannel opening associated with Prostaglandin E(2) release is adaptively regulated by mechanical stimulation","volume":"2","author":"Burra","year":"2009","journal-title":"Commun. Integr. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1093\/abbs\/gmq047","article-title":"Connexin 43 hemichannel regulates H9c2 cell proliferation by modulating intracellular ATP and [Ca2+]","volume":"42","author":"Song","year":"2010","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1002\/glia.20728","article-title":"Adhesive properties of connexin hemichannels","volume":"56","author":"Cotrina","year":"2008","journal-title":"Glia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1126\/science.1060101","article-title":"Hemichannel-mediated inhibition in the outer retina","volume":"292","author":"Kamermans","year":"2001","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1152\/physrev.00034.2009","article-title":"Lens gap junctions in growth, differentiation, and homeostasis","volume":"90","author":"Mathias","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fphys.2014.00020","article-title":"Connexin hemichannels in the lens","volume":"5","author":"Beyer","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E7194","DOI":"10.1073\/pnas.1616061113","article-title":"Critical role of ATP-induced ATP release for Ca2+ signaling in nonsensory cell networks of the developing cochlea","volume":"113","author":"Ceriani","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1523\/JNEUROSCI.3875-09.2010","article-title":"Developmental regulation of spontaneous activity in the Mammalian cochlea","volume":"30","author":"Tritsch","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1002\/jbmr.1917","article-title":"Connexin 43 channels protect osteocytes against oxidative stress-induced cell death","volume":"28","author":"Kar","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1083\/jcb.151.4.931","article-title":"Connexin43 deficiency causes delayed ossification, craniofacial abnormalities, and osteoblast dysfunction","volume":"151","author":"Lecanda","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"355","DOI":"10.4248\/BR201304006","article-title":"Elevated Intracellular Ca2+ Signals by Oxidative Stress Activate Connexin 43 Hemichannels in Osteocytes","volume":"1","author":"Riquelme","year":"2013","journal-title":"Bone Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zeng, Y., Riquelme, M.A., Hua, R., Zhang, J., Acosta, F.M., Gu, S., and Jiang, J.X. (2022). Mechanosensitive piezo1 calcium channel activates connexin 43 hemichannels through PI3K signaling pathway in bone. Cell Biosci., 12.","DOI":"10.1186\/s13578-022-00929-w"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1083\/jcb.148.5.1063","article-title":"Physiological role of gap-junctional hemichannels. Extracellular calcium-dependent isosmotic volume regulation","volume":"148","author":"Quist","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1038\/jcbfm.2011.86","article-title":"Connexin channels provide a target to manipulate brain endothelial calcium dynamics and blood-brain barrier permeability","volume":"31","author":"Culot","year":"2011","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3389\/fncel.2014.00242","article-title":"Hemichannels in neurodegenerative diseases: Is there a link to pathology?","volume":"8","author":"Bosch","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1177\/1073858414523320","article-title":"Novel astrocyte targets: New avenues for the therapeutic treatment of epilepsy","volume":"21","author":"Crunelli","year":"2015","journal-title":"Neuroscientist"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3389\/fncel.2015.00267","article-title":"Diseases associated with leaky hemichannels","volume":"9","author":"Retamal","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fphys.2014.00193","article-title":"Hemichannels: New roles in astroglial function","volume":"5","author":"Orellana","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1096\/fj.11-198416","article-title":"Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala","volume":"26","author":"Stehberg","year":"2012","journal-title":"FASEB J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9064","DOI":"10.1523\/JNEUROSCI.2204-16.2017","article-title":"Contribution of Astroglial Cx43 Hemichannels to the Modulation of Glutamatergic Currents by D-Serine in the Mouse Prefrontal Cortex","volume":"37","author":"Meunier","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/ncb2934","article-title":"Connexins modulate autophagosome biogenesis","volume":"16","author":"Bejarano","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3389\/fphys.2014.00237","article-title":"Possible role of hemichannels in cancer","volume":"5","author":"Schalper","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00395-017-0618-1","article-title":"Mitochondrial Cx43 hemichannels contribute to mitochondrial calcium entry and cell death in the heart","volume":"112","author":"Gadicherla","year":"2017","journal-title":"Basic Res. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/cvr\/cvp157","article-title":"Connexin43 in cardiomyocyte mitochondria contributes to mitochondrial potassium uptake","volume":"83","author":"Agullo","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"9726","DOI":"10.1073\/pnas.0603372103","article-title":"Properties of mouse connexin 30.2 and human connexin 31.9 hemichannels: Implications for atrioventricular conduction in the heart","volume":"103","author":"Bukauskas","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e137752","DOI":"10.1172\/JCI137752","article-title":"Cx43 hemichannel microdomain signaling at the intercalated disc enhances cardiac excitability","volume":"131","author":"Lissoni","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/cvr\/cvw215","article-title":"At the cross-point of connexins, calcium, and ATP: Blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries","volume":"113","author":"Bol","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kuang, Y., Zorzi, V., Buratto, D., Ziraldo, G., Mazzarda, F., Peres, C., Nardin, C., Salvatore, A.M., Chiani, F., and Scavizzi, F. (2020). A potent antagonist antibody targeting connexin hemichannels alleviates Clouston syndrome symptoms in mutant mice. EBioMedicine, 57.","DOI":"10.1016\/j.ebiom.2020.102825"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11388","DOI":"10.1073\/pnas.1434298100","article-title":"Gating and regulation of connexin 43 (Cx43) hemichannels","volume":"100","author":"Contreras","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/s004240000294","article-title":"Electrical properties of gap junction hemichannels identified in transfected HeLa cells","volume":"440","author":"Valiunas","year":"2000","journal-title":"Pflugers Arch."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fphys.2014.00080","article-title":"Connexin and Pannexin hemichannels are regulated by redox potential","volume":"5","author":"Retamal","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1091\/mbc.e06-03-0182","article-title":"Connexin hemichannels and gap junction channels are differentially influenced by lipopolysaccharide and basic fibroblast growth factor","volume":"18","author":"Decrock","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1083\/jcb.134.4.1019","article-title":"Properties and regulation of gap junctional hemichannels in the plasma membranes of cultured cells","volume":"134","author":"Li","year":"1996","journal-title":"J. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"C1389","DOI":"10.1152\/ajpcell.00220.2004","article-title":"Connexins are mechanosensitive","volume":"287","author":"Bao","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3389\/fphys.2013.00292","article-title":"ATP releasing connexin 30 hemichannels mediate flow-induced calcium signaling in the collecting duct","volume":"4","author":"Svenningsen","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.1074\/jbc.274.6.3711","article-title":"Regulation of connexin channels by pH. Direct action of the protonated form of taurine and other aminosulfonates","volume":"274","author":"Bevans","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3921","DOI":"10.1113\/jphysiol.2010.192096","article-title":"CO2-dependent opening of connexin 26 and related beta connexins","volume":"588","author":"Huckstepp","year":"2010","journal-title":"J. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1085\/jgp.113.5.721","article-title":"Rapid and direct effects of pH on connexins revealed by the connexin46 hemichannel preparation","volume":"113","author":"Trexler","year":"1999","journal-title":"J. Gen. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.cardiores.2003.12.030","article-title":"Structural bases for the chemical regulation of Connexin43 channels","volume":"62","author":"Delmar","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1085\/jgp.200509397","article-title":"Regulation of connexin hemichannels by monovalent cations","volume":"127","author":"Srinivas","year":"2006","journal-title":"J. Gen. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0006-3495(03)74848-6","article-title":"Effect of external magnesium and calcium on human connexin46 hemichannels","volume":"84","author":"Ebihara","year":"2003","journal-title":"Biophys. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"16030","DOI":"10.1073\/pnas.2530348100","article-title":"Molecular basis of calcium regulation in connexin-32 hemichannels","volume":"100","author":"Larrosa","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"E7986","DOI":"10.1073\/pnas.1609378113","article-title":"Mechanism of gating by calcium in connexin hemichannels","volume":"113","author":"Lopez","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1093\/hmg\/ddx386","article-title":"Cx32 hemichannel opening by cytosolic Ca2+ is inhibited by the R220X mutation that causes Charcot-Marie-Tooth disease","volume":"27","author":"Carrer","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ceca.2009.07.002","article-title":"Ca2+ regulation of connexin 43 hemichannels in C6 glioma and glial cells","volume":"46","author":"Wang","year":"2009","journal-title":"Cell Calcium"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/j.biocel.2008.01.019","article-title":"Extracellular calcium as an integrator of tissue function","volume":"40","author":"Breitwieser","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/273377a0","article-title":"Very low calcium content of cochlear endolymph, an extracellular fluid","volume":"273","author":"Bosher","year":"1978","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1085\/jgp.201210893","article-title":"Insights on the mechanisms of Ca2+ regulation of connexin26 hemichannels revealed by human pathogenic mutations (D50N\/Y)","volume":"142","author":"Lopez","year":"2013","journal-title":"J. Gen. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1085\/jgp.200409023","article-title":"Polyvalent Cations Constitute the Voltage Gating Particle in Human Connexin37 Hemichannels","volume":"124","author":"Puljung","year":"2004","journal-title":"J. Gen. Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fphys.2017.00038","article-title":"On Biophysical Properties and Sensitivity to Gap Junction Blockers of Connexin 39 Hemichannels Expressed in HeLa Cells","volume":"8","author":"Vargas","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"22139","DOI":"10.1074\/jbc.M111.240002","article-title":"Atomic force microscopy of Connexin40 gap junction hemichannels reveals calcium-dependent three-dimensional molecular topography and open-closed conformations of both the extracellular and cytoplasmic faces","volume":"286","author":"Allen","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00424-012-1133-8","article-title":"Regulation of Cx45 hemichannels mediated by extracellular and intracellular calcium","volume":"464","author":"Bader","year":"2012","journal-title":"Pflugers Arch."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s004240050788","article-title":"Gating of cx46 gap junction hemichannels by calcium and voltage","volume":"437","author":"Pfahnl","year":"1999","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1515\/BC.2006.076","article-title":"The gating effect of calmodulin and calcium on the connexin50 hemichannel","volume":"387","author":"Zhang","year":"2006","journal-title":"Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1074\/jbc.RA117.001348","article-title":"Cataract-associated Connexin 46 Mutation Alters Its Interaction with Calmodulin and Function of Hemichannels","volume":"293","author":"Hu","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"ra8","DOI":"10.1126\/scisignal.2002160","article-title":"Extracellular Ca2+ Acts as a Mediator of Communication from Neurons to Glia","volume":"5","author":"Torres","year":"2012","journal-title":"Science Signal."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e99839","DOI":"10.15252\/embj.201899839","article-title":"Coordinated calcium signalling in cochlear sensory and non-sensory cells refines afferent innervation of outer hair cells","volume":"38","author":"Ceriani","year":"2019","journal-title":"EMBO J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"265","DOI":"10.5021\/ad.2018.30.3.265","article-title":"Skin Barrier and Calcium","volume":"30","author":"Lee","year":"2018","journal-title":"Ann. Dermatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3598","DOI":"10.1093\/emboj\/cdf365","article-title":"Conformational changes in surface structures of isolated connexin 26 gap junctions","volume":"21","author":"Muller","year":"2002","journal-title":"EMBO J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1023\/B:CEMN.0000036403.43484.3d","article-title":"Properties of connexin26 hemichannels expressed in Xenopus oocytes","volume":"24","author":"Ripps","year":"2004","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.bbrc.2014.01.063","article-title":"Role of gamma carboxylated Glu47 in connexin 26 hemichannel regulation by extracellular Ca2+: Insight from a local quantum chemistry study","volume":"445","author":"Zonta","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.bbrc.2013.05.118","article-title":"Conserved glycine at position 45 of major cochlear connexins constitutes a vital component of the Ca2+ sensor for gating of gap junction hemichannels","volume":"436","author":"Zhang","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"15851","DOI":"10.1038\/s41598-017-15975-5","article-title":"Calcium binding and voltage gating in Cx46 hemichannels","volume":"7","author":"Pinto","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1080\/073911012010525027","article-title":"Permeation pathway of homomeric connexin 26 and connexin 30 channels investigated by molecular dynamics","volume":"29","author":"Zonta","year":"2012","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.neuropharm.2013.03.040","article-title":"Regulation of connexin hemichannel activity by membrane potential and the extracellular calcium in health and disease","volume":"75","author":"Fasciani","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Choi, E.J., Palacios-Prado, N., Saez, J.C., and Lee, J. (2020). Identification of Cx45 as a Major Component of GJs in HeLa Cells. Biomolecules, 10.","DOI":"10.3390\/biom10101389"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1085\/jgp.200810029","article-title":"Divalent cations regulate connexin hemichannels by modulating intrinsic voltage-dependent gating","volume":"132","author":"Verselis","year":"2008","journal-title":"J. Gen. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1016\/S0006-3495(02)75550-1","article-title":"Hemichannel and junctional properties of connexin 50","volume":"82","author":"Beahm","year":"2002","journal-title":"Biophys. J."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Bootman, M.D., and Bultynck, G. (2020). Fundamentals of Cellular Calcium Signaling: A Primer. Cold Spring Harb. Perspect. Biol., 12.","DOI":"10.1101\/cshperspect.a038802"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.molcel.2017.05.028","article-title":"Intracellular Ca2+ Sensing: Its Role in Calcium Homeostasis and Signaling","volume":"66","author":"Bagur","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"C1806","DOI":"10.1152\/ajpcell.00630.2006","article-title":"Intracellular calcium regulation of connexin43","volume":"293","author":"Lurtz","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.bbamem.2012.12.006","article-title":"Linoleic acid induces opening of connexin26 hemichannels through a PI3K\/Akt\/Ca2+-dependent pathway","volume":"1828","author":"Figueroa","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1091\/mbc.e07-12-1240","article-title":"Connexin hemichannel composition determines the FGF-1-induced membrane permeability and free [Ca2+]i responses","volume":"19","author":"Schalper","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Lagos-Cabre, R., Brenet, M., Diaz, J., Perez, R.D., Perez, L.A., Herrera-Molina, R., Quest, A.F.G., and Leyton, L. (2018). Intracellular Ca2+ Increases and Connexin 43 Hemichannel Opening Are Necessary but Not Sufficient for Thy-1-Induced Astrocyte Migration. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082179"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.neuron.2005.04.024","article-title":"ATP released via gap junction hemichannels from the pigment epithelium regulates neural retinal progenitor proliferation","volume":"46","author":"Pearson","year":"2005","journal-title":"Neuron"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00395-012-0309-x","article-title":"Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia\/reperfusion injury","volume":"108","author":"Wang","year":"2013","journal-title":"Basic Res. Cardiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s00395-012-0304-2","article-title":"Connexin mimetic peptides inhibit Cx43 hemichannel opening triggered by voltage and intracellular Ca2+ elevation","volume":"107","author":"Wang","year":"2012","journal-title":"Basic. Res. Cardiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0143-4160(02)00180-X","article-title":"Photoliberating inositol-1,4,5-trisphosphate triggers ATP release that is blocked by the connexin mimetic peptide gap 26","volume":"33","author":"Braet","year":"2003","journal-title":"Cell Calcium"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"9840","DOI":"10.1073\/pnas.152588599","article-title":"Intercellular calcium signaling mediated by point-source burst release of ATP","volume":"99","author":"Arcuino","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Van Campenhout, R., Gomes, A.R., De Groof, T.W.M., Muyldermans, S., Devoogdt, N., and Vinken, M. (2021). Mechanisms Underlying Connexin Hemichannel Activation in Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073503"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e2213162119","DOI":"10.1073\/pnas.2213162119","article-title":"Inhibition of connexin hemichannels alleviates neuroinflammation and hyperexcitability in temporal lobe epilepsy","volume":"119","author":"Guo","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Gonzalez-Jamett, A., Vasquez, W., Cifuentes-Riveros, G., Martinez-Pando, R., Saez, J.C., and Cardenas, A.M. (2022). Oxidative Stress, Inflammation and Connexin Hemichannels in Muscular Dystrophies. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020507"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neulet.2017.09.020","article-title":"Connexin hemichannels and cochlear function","volume":"695","author":"Verselis","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.jid.2015.11.017","article-title":"From Hyperactive Connexin26 Hemichannels to Impairments in Epidermal Calcium Gradient and Permeability Barrier in the Keratitis-Ichthyosis-Deafness Syndrome","volume":"136","author":"Garcia","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3389\/fnmol.2018.00227","article-title":"What\u2019s the Function of Connexin 32 in the Peripheral Nervous System?","volume":"11","author":"Bortolozzi","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1091\/mbc.E16-01-0062","article-title":"Specific functional pathologies of Cx43 mutations associated with oculodentodigital dysplasia","volume":"27","author":"Kelly","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"6564","DOI":"10.1093\/hmg\/ddv365","article-title":"Exome sequencing reveals mutation in GJA1 as a cause of keratoderma-hypotrichosis-leukonychia totalis syndrome","volume":"24","author":"Wang","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Lucaciu, S.A., Figliuzzi, R., Neumann, R., Nazarali, S., Del Sordo, L., Leighton, S.E., Hauser, A., Shao, Q., Johnston, D., and Bai, D. (2023). GJB4 variants linked to skin disease exhibit a trafficking deficiency en route to gap junction formation that can be restored by co-expression of select connexins. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1073805"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fphar.2013.00043","article-title":"Connexin mutants and cataracts","volume":"4","author":"Beyer","year":"2013","journal-title":"Front. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Prieto-Villalobos, J., Alvear, T.F., Liberona, A., Lucero, C.M., Martinez-Araya, C.J., Balmazabal, J., Inostroza, C.A., Ramirez, G., Gomez, G.I., and Orellana, J.A. (2021). Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179503"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Lucero, C.M., Prieto-Villalobos, J., Marambio-Ruiz, L., Balmazabal, J., Alvear, T.F., Vega, M., Barra, P., Retamal, M.A., Orellana, J.A., and Gomez, G.I. (2022). Hypertensive Nephropathy: Unveiling the Possible Involvement of Hemichannels and Pannexons. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415936"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00232-007-9055-7","article-title":"Some oculodentodigital dysplasia-associated Cx43 mutations cause increased hemichannel activity in addition to deficient gap junction channels","volume":"219","author":"Dobrowolski","year":"2007","journal-title":"J. Membr. Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/jid.2008.335","article-title":"Connexin mutations causing skin disease and deafness increase hemichannel activity and cell death when expressed in Xenopus oocytes","volume":"129","author":"Lee","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"C506","DOI":"10.1152\/ajpcell.00353.2013","article-title":"Cx46 hemichannels contribute to the sodium leak conductance in lens fiber cells","volume":"306","author":"Ebihara","year":"2014","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1089\/ars.2008.2138","article-title":"Gap-junction channels dysfunction in deafness and hearing loss","volume":"11","author":"Martinez","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.bbamem.2012.06.024","article-title":"The role of connexins in ear and skin physiology-functional insights from disease-associated mutations","volume":"1828","author":"Xu","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.bbrc.2010.03.073","article-title":"Connexin 26 (GJB2) mutations, causing KID Syndrome, are associated with cell death due to calcium gating deregulation","volume":"394","author":"Terrinoni","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1085\/jgp.201711782","article-title":"The syndromic deafness mutation G12R impairs fast and slow gating in Cx26 hemichannels","volume":"150","author":"Garcia","year":"2018","journal-title":"J. Gen. Physiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1038\/jid.2015.20","article-title":"Keratitis-ichthyosis-deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43","volume":"135","author":"Garcia","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"9721","DOI":"10.1074\/jbc.M116.770917","article-title":"Induction of cell death and gain-of-function properties of connexin26 mutants predict severity of skin disorders and hearing loss","volume":"292","author":"Press","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1085\/jgp.201812219","article-title":"The connexin26 human mutation N14K disrupts cytosolic intersubunit interactions and promotes channel opening","volume":"151","author":"Chatterjee","year":"2019","journal-title":"J. Gen. Physiol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Aypek, H., Bay, V., and Mese, G. (2016). Altered cellular localization and hemichannel activities of KID syndrome associated connexin26 I30N and D50Y mutations. BMC Cell Biol., 17.","DOI":"10.1186\/s12860-016-0081-0"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1085\/jgp.201010433","article-title":"Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause keratitis ichthyosis deafness syndrome","volume":"136","author":"Sanchez","year":"2010","journal-title":"J. Gen. Physiol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"C1150","DOI":"10.1152\/ajpcell.00374.2012","article-title":"The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity","volume":"304","author":"Mhaske","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1096\/fj.04-3491fje","article-title":"Mechanism of the defect in gap-junctional communication by expression of a connexin 26 mutant associated with dominant deafness","volume":"19","author":"Chen","year":"2005","journal-title":"FASEB J."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1016\/j.febslet.2015.05.047","article-title":"Altered epidermal lipid processing and calcium distribution in the KID syndrome mouse model Cx26S17F","volume":"589","author":"Bosen","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4161\/chan.26789","article-title":"Divalent regulation and intersubunit interactions of human Connexin26 (Cx26) hemichannels","volume":"8","author":"Lopez","year":"2014","journal-title":"Channels"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Abbott, A.C., Garcia, I.E., Villanelo, F., Flores-Munoz, C., Ceriani, R., Maripillan, J., Novoa-Molina, J., Figueroa-Cares, C., Perez-Acle, T., and Saez, J.C. (2022). Expression of KID syndromic mutation Cx26S17F produces hyperactive hemichannels in supporting cells of the organ of Corti. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1071202"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1091\/mbc.e11-12-1058","article-title":"Critical role of the first transmembrane domain of Cx26 in regulating oligomerization and function","volume":"23","author":"Jara","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1097\/01.mlg.0000241944.77192.d2","article-title":"A novel mechanism for connexin 26 mutation linked deafness: Cell death caused by leaky gap junction hemichannels","volume":"116","author":"Stong","year":"2006","journal-title":"Laryngoscope"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1093\/hmg\/ddh191","article-title":"Connexin30 mutations responsible for hidrotic ectodermal dysplasia cause abnormal hemichannel activity","volume":"13","author":"Essenfelder","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"3980","DOI":"10.1073\/pnas.261713499","article-title":"Voltage opens unopposed gap junction hemichannels formed by a connexin 32 mutant associated with X-linked Charcot-Marie-Tooth disease","volume":"99","author":"Abrams","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41598-018-37221-2","article-title":"Connexin43 mutations linked to skin disease have augmented hemichannel activity","volume":"9","author":"Srinivas","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1242\/jcs.02770","article-title":"Oculodentodigital dysplasia connexin43 mutations result in non-functional connexin hemichannels and gap junctions in C6 glioma cells","volume":"119","author":"Lai","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"4378","DOI":"10.1096\/fj.09-153007","article-title":"Intramolecular loop\/tail interactions are essential for connexin 43-hemichannel activity","volume":"24","author":"Ponsaerts","year":"2010","journal-title":"FASEB J."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"C596","DOI":"10.1152\/ajpcell.2000.279.3.C596","article-title":"Connexin46 mutations linked to congenital cataract show loss of gap junction channel function","volume":"279","author":"Pal","year":"2000","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Ren, Q., Riquelme, M.A., Xu, J., Yan, X., Nicholson, B.J., Gu, S., and Jiang, J.X. (2013). Cataract-causing mutation of human connexin 46 impairs gap junction, but increases hemichannel function and cell death. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074732"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1126\/science.8266101","article-title":"Connexin mutations in X-linked Charcot-Marie-Tooth disease","volume":"262","author":"Bergoffen","year":"1993","journal-title":"Science"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Zheng, L., Chenavas, S., Kieken, F., Trease, A., Brownell, S., Anbanandam, A., Sorgen, P.L., and Spagnol, G. (2020). Calmodulin Directly Interacts with the Cx43 Carboxyl-Terminus and Cytoplasmic Loop Containing Three ODDD-Linked Mutants (M147T, R148Q, and T154A) that Retain alpha-Helical Structure, but Exhibit Loss-of-Function and Cellular Trafficking Defects. Biomolecules, 10.","DOI":"10.3390\/biom10101452"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"851","DOI":"10.2174\/156652410793937750","article-title":"Gap junctions or hemichannel-dependent and independent roles of connexins in cataractogenesis and lens development","volume":"10","author":"Jiang","year":"2010","journal-title":"Curr. Mol. Med."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Villanelo, F., Carrasco, J., Jensen-Flores, J., Garate, J.A., and Perez-Acle, T. (2021). Simulations on Simple Models of Connexin Hemichannels Indicate That Ca2+ Blocking Is Not a Pure Electrostatic Effect. Membranes, 11.","DOI":"10.3390\/membranes11050372"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Jagielnicki, M., Kucharska, I., Bennett, B.C., Harris, A.L., and Yeager, M. (2024). Connexin Gap Junction Channels and Hemichannels: Insights from High-Resolution Structures. Biology, 13.","DOI":"10.3390\/biology13050298"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3389\/fnmol.2018.00170","article-title":"Cues to Opening Mechanisms From in Silico Electric Field Excitation of Cx26 Hemichannel and in Vitro Mutagenesis Studies in HeLa Transfectans","volume":"11","author":"Zonta","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"eaba4996","DOI":"10.1126\/sciadv.aba4996","article-title":"Cryo-EM structure of human Cx31.3\/GJC3 connexin hemichannel","volume":"6","author":"Lee","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e14086","DOI":"10.1111\/apha.14086","article-title":"IP3RPEP6, a novel peptide inhibitor of IP(3) receptor channels that does not affect connexin-43 hemichannels","volume":"240","author":"Tao","year":"2024","journal-title":"Acta Physiol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1006\/meth.1999.0936","article-title":"Chemical gating of gap junction channels","volume":"20","author":"Peracchia","year":"2000","journal-title":"Methods"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"C1384","DOI":"10.1152\/ajpcell.1998.275.5.C1384","article-title":"Molecular dissection of a basic COOH-terminal domain of Cx32 that inhibits gap junction gating sensitivity","volume":"275","author":"Wang","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1016\/j.bpj.2008.12.3941","article-title":"Calmodulin mediates the Ca2+-dependent regulation of Cx44 gap junctions","volume":"96","author":"Zhou","year":"2009","journal-title":"Biophys. J."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Peracchia, C. (2000). Behavior of chemical- and slow voltage-sensitive gating of connexin channels: The \u201ccork\u201d gating hypothesis. Gap Junctions. Molecular Basis of Cell Communication in Health and Disease, Academic Press.","DOI":"10.1016\/S0070-2161(08)61017-5"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Lissoni, A., Wang, N., Nezlobinskii, T., De Smet, M., Panfilov, A.V., Vandersickel, N., Leybaert, L., and Witschas, K. (2020). Gap19, a Cx43 Hemichannel Inhibitor, Acts as a Gating Modifier That Decreases Main State Opening While Increasing Substate Gating. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197340"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/boc.201100079","article-title":"The contractile system as a negative regulator of the connexin 43 hemichannel","volume":"104","author":"Ponsaerts","year":"2012","journal-title":"Biol. Cell"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Peracchia, C., and Peracchia, L.M.L. (2021). Calmodulin-Connexin Partnership in Gap Junction Channel Regulation-Calmodulin-Cork Gating Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313055"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Tran, O., Kerruth, S., Coates, C., Kaur, H., Peracchia, C., Carter, T., and Torok, K. (2023). Ca2+-Dependent and -Independent Calmodulin Binding to the Cytoplasmic Loop of Gap Junction Connexins. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044153"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1042\/bj3260479","article-title":"Connexin 32 of gap junctions contains two cytoplasmic calmodulin-binding domains","volume":"326","author":"Torok","year":"1997","journal-title":"Biochem. J."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1046\/j.1432-1327.2001.02380.x","article-title":"Assembly of gap junction channels: Mechanism, effects of calmodulin antagonists and identification of connexin oligomerization determinants","volume":"268","author":"Ahmad","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3389\/fnins.2014.00151","article-title":"CamKII inhibitors reduce mitotic instability, connexon anomalies and progression of the in vivo behavioral phenotype in transgenic animals expressing a mutated Gjb1 gene","volume":"8","author":"Mones","year":"2014","journal-title":"Front. Neurosci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fncel.2016.00049","article-title":"CMTX Disorder and CamKinase","volume":"10","author":"Bihel","year":"2016","journal-title":"Front. Cell. Neurosci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1080\/17460441.2020.1773787","article-title":"Peptide-based targeting of connexins and pannexins for therapeutic purposes","volume":"15","author":"Caufriez","year":"2020","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Buratto, D., Donati, V., Zonta, F., and Mammano, F. (2021). Harnessing the therapeutic potential of antibodies targeting connexin hemichannels. Biochim. Biophys. Acta Mol. Basis Dis., 1867.","DOI":"10.1016\/j.bbadis.2020.166047"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1021\/acsmedchemlett.8b00158","article-title":"Inhibition of Connexin Hemichannels by New Amphiphilic Aminoglycosides without Antibiotic Activity","volume":"9","author":"AlFindee","year":"2018","journal-title":"ACS Med. Chem. 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