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 (Cx23, Cx25, Cx26, Cx30, Cx30.2, Cx30.3, Cx31, Cx31.1, Cx31.9, Cx32, Cx36, Cx37, Cx40, Cx40.1, Cx43, Cx45, Cx46, Cx47, Cx50, Cx59, Cx62) and 3 pannexin genes (Px1, Px2, Px3; 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].
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
|
Cx23
Show »« Hide
| Nomenclature |
Cx23
|
| Other names |
CX23,
LOC308377_predicted,
LOC681263,
RGD1308189,
RGD1308189_predicted,
gap junction epsilon-1 protein,
similar to connexin 39,
similar to connexin 62 (predicted),
AEY12,
connexin 23,
Gjf1,
Gsfaey12
|
| Genes |
GJE1 (Hs), Gje1 (Mm), Gje1 (Rn) |
| Ensembl ID |
ENSG00000203733 (Hs), ENSMUSG00000019867 (Mm), ENSRNOG00000012092 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx25
Show »« Hide
| Nomenclature |
Cx25
|
| Other names |
CX25,
bA136M9.1,
gap junction protein, beta 7,
connexin 25
|
| Genes |
GJB7 (Hs) |
| Ensembl ID |
ENSG00000164411 (Hs)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx26
Show »« Hide
| Nomenclature |
Cx26
|
| Other names |
DFNB1,
DFNA3,
CX26,
NSRD1,
gap junction protein, beta 2, 26kD (connexin 26),
gap junction protein, beta 2, 26kDa (connexin 26),
connexin 26,
CXN-26,
MGC93804,
connexin-26,
gap junction beta-2 protein,
gap junction channel protein connexin 26,
gap junction membrane channel protein beta 2,
gap junction protein, beta 2,
Gjb-2
|
| Genes |
GJB2 (Hs), Gjb2 (Mm), Gjb2 (Rn) |
| Ensembl ID |
ENSG00000165474 (Hs), ENSMUSG00000046352 (Mm), ENSRNOG00000008855 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx30
Show »« Hide
| Nomenclature |
Cx30
|
| Other names |
DFNA3,
ED2,
EDH,
HED,
CX30,
ectodermal dysplasia 2, hidrotic (Clouston syndrome),
gap junction protein, beta 6 (connexin 30),
gap junction protein, beta 6,
connexin 30,
gap junction beta-6 protein,
gap junction membrane channel protein beta 6,
D14Bwg0506e
|
| Genes |
GJB6 (Hs), Gjb6 (Mm), Gjb6 (Rn) |
| Ensembl ID |
ENSG00000121742 (Hs), ENSMUSG00000040055 (Mm), ENSRNOG00000022116 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx30.2
Show »« Hide
| Nomenclature |
Cx30.2
|
| Other names |
GJE1,
CX30.2,
gap junction protein, epsilon 1, 29kDa,
connexin 30.2,
Cx29,
connexin 29,
gap junction gamma-3 protein,
gap junction membrane channel protein epsilon 1,
gap junction protein, gamma 3
|
| Genes |
GJC3 (Hs), Gjc3 (Mm), Gjc3 (Rn) |
| Ensembl ID |
ENSG00000176402 (Hs), ENSMUSG00000056966 (Mm), ENSRNOG00000001329 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx30.3
Show »« Hide
| Nomenclature |
Cx30.3
|
| Other names |
CX30.3,
gap junction protein, beta 4 (connexin 30.3),
gap junction protein, beta 4,
connexin 30.3,
Cnx30.3,
connexin-30.3,
gap junction beta-4 protein,
gap junction membrane channel protein beta 4,
Gjb-4
|
| Genes |
GJB4 (Hs), Gjb4 (Mm), Gjb4 (Rn) |
| Ensembl ID |
ENSG00000189433 (Hs), ENSMUSG00000046623 (Mm), ENSRNOG00000026910 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx31
Show »« Hide
| Nomenclature |
Cx31
|
| Other names |
DFNA2,
EKV,
CX31,
gap junction protein, beta 3, 31kD (connexin 31),
gap junction protein, beta 3, 31kDa (connexin 31),
erythrokeratodermia variabilis,
connexin 31,
connexin-31,
gap junction beta-3 protein,
gap junction membrane channel protein beta 3,
gap junction protein, beta 3,
Cnx31,
Gjb-3,
D4Wsu144e
|
| Genes |
GJB3 (Hs), Gjb3 (Mm), Gjb3 (Rn) |
| Ensembl ID |
ENSG00000188910 (Hs), ENSMUSG00000042367 (Mm), ENSRNOG00000014372 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx31.1
Show »« Hide
| Nomenclature |
Cx31.1
|
| Other names |
CX31.1,
gap junction protein, beta 5 (connexin 31.1),
gap junction protein, beta 5,
connexin 31.1,
connexin-31.1,
gap junction beta-5 protein,
gap junction membrane channel protein beta 5,
Cnx31.1,
Gjb-5
|
| Genes |
GJB5 (Hs), Gjb5 (Mm), Gjb5 (Rn) |
| Ensembl ID |
ENSG00000189280 (Hs), ENSMUSG00000042357 (Mm), ENSRNOG00000014408 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx31.9
Show »« Hide
| Nomenclature |
Cx31.9
|
| Other names |
GJC1,
CX31.9,
GJA11,
Cx30.2,
gap junction protein, chi 1, 31.9kDa,
connexin 31.9,
Gjc1_predicted,
LOC363677,
connexin30.2,
gap junction delta-3 protein,
gap junction membrane channel protein chi 1,
gap junction membrane channel protein chi 1 (predicted),
gap junction protein, delta 3,
connexin-30.2,
connexin 30.2
|
| Genes |
GJD3 (Hs), Gjd3 (Mm), Gjd3 (Rn) |
| Ensembl ID |
ENSG00000183153 (Hs), ENSMUSG00000047197 (Mm), ENSRNOG00000027688 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx32
Show »« Hide
| Nomenclature |
Cx32
|
| Other names |
CMTX1,
CMTX,
CX32,
gap junction protein, beta 1, 32kD (connexin 32, Charcot-Marie-Tooth neuropathy, X-linked),
gap junction protein, beta 1, 32kDa (connexin 32, Charcot-Marie-Tooth neuropathy, X-linked),
gap junction protein, beta 1, 32kDa (connexin 32),
Charcot-Marie-Tooth neuropathy, X-linked,
connexin 32,
GAP junction 28 kDa liver protein,
connexin-32,
gap junction beta-1 protein,
gap junction membrane channel protein beta 1,
Gjb-1
|
| Genes |
GJB1 (Hs), Gjb1 (Mm), Gjb1 (Rn) |
| Ensembl ID |
ENSG00000169562 (Hs), ENSMUSG00000047797 (Mm), ENSRNOG00000003746 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx36
Show »« Hide
| Nomenclature |
Cx36
|
| Other names |
GJA9,
CX36,
gap junction protein, alpha 9, 36kDa,
connexin 36,
connexin-36,
gap junction alpha-9 protein,
gap junction delta-2 protein,
gap junction membrane channel protein alpha 9,
gap junction protein, delta 2,
connexin36
|
| Genes |
GJD2 (Hs), Gjd2 (Mm), Gjd2 (Rn) |
| Ensembl ID |
ENSG00000159248 (Hs), ENSMUSG00000068615 (Mm), ENSRNOG00000008337 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx37
Show »« Hide
| Nomenclature |
Cx37
|
| Other names |
CX37,
gap junction protein, alpha 4, 37kD (connexin 37),
gap junction protein, alpha 4, 37kDa (connexin 37),
connexin 37,
CXN37,
Gap junction membrane channel protein alpha 4 (connexin 37),
Gap junction membrane channel, protein alpha 4 (connexin 37),
connexin-37,
gap junction alpha-4 protein,
gap junction membrane channel protein alpha 4,
gap junction protein, alpha 4,
Cnx37,
Gja-4
|
| Genes |
GJA4 (Hs), Gja4 (Mm), Gja4 (Rn) |
| Ensembl ID |
ENSG00000187513 (Hs), ENSMUSG00000050234 (Mm), ENSRNOG00000014357 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx40
Show »« Hide
| Nomenclature |
Cx40
|
| Other names |
CX40,
gap junction protein, alpha 5, 40kD (connexin 40),
gap junction protein, alpha 5, 40kDa (connexin 40),
connexin 40,
connexin-40,
gap junction alpha-5 protein,
gap junction membrane channel protein alpha 5,
gap junction membrane channel protein alpha 5 (connexin 40),
gap junction protein, alpha 5,
Gja-5
|
| Genes |
GJA5 (Hs), Gja5 (Mm), Gja5 (Rn) |
| Ensembl ID |
ENSG00000143140 (Hs), ENSMUSG00000057123 (Mm), ENSRNOG00000017484 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx40.1
Show »« Hide
| Nomenclature |
Cx40.1
|
| Other names |
CX40.1,
FLJ90023,
connexin 40.1,
Cx39,
connexin 39,
gap junction channel protein,
gap junction protein, delta 4
|
| Genes |
GJD4 (Hs), Gjd4 (Mm), Gjd4 (Rn) |
| Ensembl ID |
ENSG00000177291 (Hs), ENSMUSG00000036855 (Mm), ENSRNOG00000018407 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx43
Show »« Hide
| Nomenclature |
Cx43
|
| Other names |
ODDD,
GJAL,
CX43,
ODD,
ODOD,
SDTY3,
gap junction protein, alpha-like,
gap junction protein, alpha 1, 43kDa (connexin 43),
oculodentodigital dysplasia (syndactyly type III),
connexin 43,
MGC93610,
Gap junction protein alpha 1 43 kD (connexin 43),
Gap junction protein, alpha 1, 43 kD (connexin 43),
connexin-43,
gap junction 43 kDa heart protein,
gap junction alpha-1 protein,
gap junction membrane channel protein alpha 1,
gap junction protein alpha 1 43 kD,
gap junction protein, alpha 1,
alpha 1 connexin,
connexin43,
Gja-1,
Cx43alpha1
|
| Genes |
GJA1 (Hs), Gja1 (Mm), Gja1 (Rn) |
| Ensembl ID |
ENSG00000152661 (Hs), ENSMUSG00000050953 (Mm), ENSRNOG00000000805 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx45
Show »« Hide
|
|
Cx46
Show »« Hide
| Nomenclature |
Cx46
|
| Other names |
CZP3,
CX46,
gap junction protein, alpha 3, 46kD (connexin 46),
gap junction protein, alpha 3, 46kDa (connexin 46),
connexin 46,
connexin-46,
gap junction alpha-3 protein,
gap junction membrane channel protein alpha 3,
gap junction protein, alpha 3,
alpha 3 connexin,
Gja-3
|
| Genes |
GJA3 (Hs), Gja3 (Mm), Gja3 (Rn) |
| Ensembl ID |
ENSG00000121743 (Hs), ENSMUSG00000048582 (Mm), ENSRNOG00000008847 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx47
Show »« Hide
| Nomenclature |
Cx47
|
| Other names |
GJA12,
CX47,
CX46.6,
SPG44,
gap junction protein, alpha 12, 47kDa,
connexin 47,
Gja12_predicted,
connexin-47,
gap junction alpha-12 protein,
gap junction gamma-2 protein,
gap junction membrane channel protein alpha 12,
gap junction protein, alpha 12,
gap junction protein, alpha 12, 47kDa (predicted)
|
| Genes |
GJC2 (Hs), Gjc2 (Mm), Gjc2 (Rn) |
| Ensembl ID |
ENSG00000198835 (Hs), ENSMUSG00000043448 (Mm), ENSRNOG00000038328 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx50
Show »« Hide
| Nomenclature |
Cx50
|
| Other names |
CAE1,
CZP1,
CAE,
CX50,
gap junction protein, alpha 8, 50kD (connexin 50),
gap junction protein, alpha 8, 50kDa (connexin 50),
connexin 50,
Cnx50,
alpha 8 connexin,
Lop10,
Aey5
|
| Genes |
GJA8 (Hs), Gja8 (Mm) |
| Ensembl ID |
ENSG00000121634 (Hs), ENSMUSG00000049908 (Mm)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx59
Show »« Hide
| Nomenclature |
Cx59
|
| Other names |
GJA10,
CX59,
CX58,
gap junction protein, alpha 10, 59kDa,
connexin 59
|
| Genes |
GJA9 (Hs) |
| Ensembl ID |
ENSG00000131233 (Hs)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Cx62
Show »« Hide
| Nomenclature |
Cx62
|
| Other names |
CX62,
connexin 62,
Cx-57,
Cx57,
Gja10_predicted,
LOC313126_predicted,
RGD1309630,
RGD1309630_predicted,
connexin 57,
gap junction membrane channel protein alpha 10,
gap junction membrane channel protein alpha 10 (predicted),
gap junction protein, alpha 10,
similar to connexin 57 (predicted),
connexin-57,
Cx59
|
| Genes |
GJA10 (Hs), Gja10 (Mm), Gja10 (Rn) |
| Ensembl ID |
ENSG00000135355 (Hs), ENSMUSG00000051056 (Mm), ENSRNOG00000006478 (Rn)
|
| Endogenous inhibitors |
|
extracellular
Ca2+
(blocked by raising external Ca2+)
|
|
| Inhibitors |
|
|
|
Px1
Show »« Hide
|
|
Px2
Show »« Hide
|
|
Px3
Show »« Hide
|
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]
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]
Goodenough, DA; Paul, DL. (2009) Gap junctions.
Cold Spring Harb Perspect Biol, 1 (1): a002576.
[PMID:20066080]
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]
Söhl, G; Maxeiner, S; Willecke, K. (2005) Expression and functions of neuronal gap junctions.
Nat. Rev. Neurosci., 6 (3): 191-200.
[PMID:15738956]
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]
@GuidetoPHARM 
Like us on Facebook 
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]).