Gap junctions are essential for many physiological processes including cardiac and smooth muscle contraction, regulation of neuronal excitability and epithelial electrolyte transport [3-5]. Gap junction channels allow the passive diffusion of molecules of up to 1,000 Daltons which can include nutrients, metabolites and second messengers (such as IP₃) as well as cations and anions. 21 connexin genes and 3 pannexin genes which are structurally related to the invertebrate innexin genes) code for gap junction proteins in humans. Each connexin gap junction comprises 2 hemichannels or 'connexons' which are themselves formed from 6 connexin molecules. The various connexins have been observed to combine into both homomeric and heteromeric combinations, each of which may exhibit different functional properties. It is also suggested that individual hemichannels formed by a number of different connexins might be functional in at least some cells [6]. Connexins have a common topology, with four α-helical transmembrane domains, two extracellular loops, a cytoplasmic loop, and N- and C-termini located on the cytoplasmic membrane face. In mice, the most abundant connexins in electrical synapses in the brain seem to be Cx36, Cx45 and Cx57 [9]. Mutations in connexin genes are associated with the occurrence of a number of pathologies, such as peripheral neuropathies, cardiovascular diseases and hereditary deafness. The pannexin genes Px1 and Px2 are widely expressed in the mammalian brain [10]. Like the connexins, at least some of the pannexins can form hemichannels [3,7].

Connexins are most commonly named according to their molecular weights, so, for example, Cx23 is the connexin protein of 23 kDa. This can cause confusion when comparing between species – for example, the mouse connexin Cx57 is orthologous to the human connexin Cx62. No natural toxin or specific inhibitor of junctional channels has been identified yet however two compounds often used experimentally to block connexins are carbenoxolone and flufenamic acid [8]. At least some pannexin hemichannels are more sensitive to carbenoxolone than connexins but much less sensitive to flufenamic acid [2]. It has been suggested that 2-aminoethoxydiphenyl borate (2-APB) may be a more effective blocker of some connexin channel subtypes (Cx26, Cx30, Cx36, Cx40, Cx45, Cx50) compared to others (Cx32, Cx43, Cx46, [1]).

* Key recommended reading is highlighted with an asterisk

Bennett MV, Zukin RS. (2004) Electrical coupling and neuronal synchronization in the Mammalian brain. Neuron, 41 (4): 495-511. [PMID:14980200]

Connors BW, Long MA. (2004) Electrical synapses in the mammalian brain. Annu. Rev. Neurosci., 27: 393-418. [PMID:15217338]

Cruciani V, Mikalsen SO. (2006) The vertebrate connexin family. Cell. Mol. Life Sci., 63 (10): 1125-40. [PMID:16568237]

* Decrock E, De Bock M, Wang N, Bultynck G, Giaume C, Naus CC, Green CR, Leybaert L. (2015) Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?. Cell. Mol. Life Sci., 72 (15): 2823-51. [PMID:26118660]

* Esseltine JL, Laird DW. (2016) Next-Generation Connexin and Pannexin Cell Biology. Trends Cell Biol., 26 (12): 944-955. [PMID:27339936]

Evans WH, De Vuyst E, Leybaert L. (2006) The gap junction cellular internet: connexin hemichannels enter the signalling limelight. Biochem. J., 397 (1): 1-14. [PMID:16761954]

Evans WH, Martin PE. (2002) Gap junctions: structure and function (Review). Mol. Membr. Biol., 19 (2): 121-36. [PMID:12126230]

* Freund-Michel V, Muller B, Marthan R, Savineau JP, Guibert C. (2016) Expression and role of connexin-based gap junctions in pulmonary inflammatory diseases. Pharmacol. Ther., 164: 105-19. [PMID:27126473]

Goodenough DA, Paul DL. (2009) Gap junctions. Cold Spring Harb Perspect Biol, 1 (1): a002576. [PMID:20066080]

* Harris AL. (2018) Electrical coupling and its channels. J. Gen. Physiol., 150 (12): 1606-1639. [PMID:30389716]

Hervé JC, Phelan P, Bruzzone R, White TW. (2005) Connexins, innexins and pannexins: bridging the communication gap. Biochim. Biophys. Acta, 1719 (1-2): 3-5. [PMID:16359939]

Hervé JC, Sarrouilhe D. (2005) Connexin-made channels as pharmacological targets. Curr. Pharm. Des., 11 (15): 1941-58. [PMID:15974969]

Hormuzdi SG, Filippov MA, Mitropoulou G, Monyer H, Bruzzone R. (2004) Electrical synapses: a dynamic signaling system that shapes the activity of neuronal networks. Biochim. Biophys. Acta, 1662 (1-2): 113-37. [PMID:15033583]

Kandouz M, Batist G. (2010) Gap junctions and connexins as therapeutic targets in cancer. Expert Opin. Ther. Targets, 14 (7): 681-92. [PMID:20446866]

Kumar NM, Gilula NB. (1996) The gap junction communication channel. Cell, 84 (3): 381-8. [PMID:8608591]

MacVicar BA, Thompson RJ. (2010) Non-junction functions of pannexin-1 channels. Trends Neurosci., 33 (2): 93-102. [PMID:20022389]

Meşe G, Richard G, White TW. (2007) Gap junctions: basic structure and function. J. Invest. Dermatol., 127 (11): 2516-24. [PMID:17934503]

Salameh A, Dhein S. (2005) Pharmacology of gap junctions. New pharmacological targets for treatment of arrhythmia, seizure and cancer?. Biochim. Biophys. Acta, 1719 (1-2): 36-58. [PMID:16216217]

Shestopalov VI, Panchin Y. (2008) Pannexins and gap junction protein diversity. Cell. Mol. Life Sci., 65 (3): 376-94. [PMID:17982731]

Spray DC, Dermietzel R. (1996) Neuroscience Intelligence Unit: Gap Junctions in the Nervous System. In  (Springer) . [ISBN:0412110318]

* Sáez JC, Cisterna BA, Vargas A, Cardozo CP. (2015) Regulation of pannexin and connexin channels and their functional role in skeletal muscles. Cell. Mol. Life Sci., 72 (15): 2929-35. [PMID:26084874]

Söhl G, Maxeiner S, Willecke K. (2005) Expression and functions of neuronal gap junctions. Nat. Rev. Neurosci., 6 (3): 191-200. [PMID:15738956]

Thompson RJ. (2015) Pannexin channels and ischaemia. J. Physiol. (Lond.), 593 (16): 3463-70. [PMID:25384783]

* Willebrords J, Maes M, Crespo Yanguas S, Vinken M. (2017) Inhibitors of connexin and pannexin channels as potential therapeutics. Pharmacol. Ther., 180: 144-160. [PMID:28720428]

Yen MR, Saier MH. (2007) Gap junctional proteins of animals: the innexin/pannexin superfamily. Prog. Biophys. Mol. Biol., 94 (1-2): 5-14. [PMID:17507077]

Zoidl G, Dermietzel R. (2010) Gap junctions in inherited human disease. Pflugers Arch., 460 (2): 451-66. [PMID:20140684]

1. Bai D, del Corsso C, Srinivas M, Spray DC. (2006) Block of specific gap junction channel subtypes by 2-aminoethoxydiphenyl borate (2-APB). J. Pharmacol. Exp. Ther., 319 (3): 1452-8. [PMID:16985167]

2. Bruzzone R, Barbe MT, Jakob NJ, Monyer H. (2005) Pharmacological properties of homomeric and heteromeric pannexin hemichannels expressed in Xenopus oocytes. J. Neurochem., 92 (5): 1033-43. [PMID:15715654]

3. Bruzzone R, Hormuzdi SG, Barbe MT, Herb A, Monyer H. (2003) Pannexins, a family of gap junction proteins expressed in brain. Proc. Natl. Acad. Sci. U.S.A., 100 (23): 13644-9. [PMID:14597722]

4. Connors BW, Long MA. (2004) Electrical synapses in the mammalian brain. Annu. Rev. Neurosci., 27: 393-418. [PMID:15217338]

5. Evans WH, Martin PE. (2002) Gap junctions: structure and function (Review). Mol. Membr. Biol., 19 (2): 121-36. [PMID:12126230]

6. Hervé JC, Bourmeyster N, Sarrouilhe D, Duffy HS. (2007) Gap junctional complexes: from partners to functions. Prog. Biophys. Mol. Biol., 94 (1-2): 29-65. [PMID:17507078]

7. Pelegrin P, Surprenant A. (2007) Pannexin-1 couples to maitotoxin- and nigericin-induced interleukin-1beta release through a dye uptake-independent pathway. J. Biol. Chem., 282 (4): 2386-94. [PMID:17121814]

8. Salameh A, Dhein S. (2005) Pharmacology of gap junctions. New pharmacological targets for treatment of arrhythmia, seizure and cancer?. Biochim. Biophys. Acta, 1719 (1-2): 36-58. [PMID:16216217]

9. Söhl G, Maxeiner S, Willecke K. (2005) Expression and functions of neuronal gap junctions. Nat. Rev. Neurosci., 6 (3): 191-200. [PMID:15738956]

10. Vogt A, Hormuzdi SG, Monyer H. (2005) Pannexin1 and Pannexin2 expression in the developing and mature rat brain. Brain Res. Mol. Brain Res., 141 (1): 113-20. [PMID:16143426]