Editing Gap junction (section)

===Form to function===
Well before the demonstration of the gap in gap junctions, they were seen at the junction of neighboring nerve cells. The close proximity of the neighboring cell membranes at the gap junction led researchers to speculate that they had a role in intercellular communication, in particular the transmission of electrical signals.<ref name="robertson" /><ref>{{Cite book|editor1-first=Michael |editor1-last=Locke |year=1963 |title=Cellular membranes in development |publisher=Academic Press |location=New York |oclc=261587041 |last1=Robertson |first1=J. D. }}{{Page needed|date=September 2010}}</ref><ref>{{Cite journal|pmid=7033238 |pmc=2112820 |title=Membrane structure |journal=The Journal of Cell Biology |year=1981 |volume=91 |issue=3 |author=Robertson |pages=189s–204s |jstor=1609517 |doi=10.1083/jcb.91.3.189s}}</ref> Gap junctions were also found to be electrically rectifying in the early studies and referred to as an [[electrical synapse]]<ref>{{Cite journal|doi=10.1038/180342a0 |title=Mechanism of Nerve-Impulse Transmission at a Crayfish Synapse |year=1957 |vauthors=Furshpan EJ, Potter DD |journal=Nature |volume=180 |pages=342–343 |pmid=13464833 |issue=4581 |bibcode=1957Natur.180..342F |s2cid=4216387}}</ref><ref>{{Cite journal |pmid=13642302 |pmc=1356828 |year=1959 |vauthors=Furshpan EJ, Potter DD |title=Transmission at the giant motor synapses of the crayfish |volume=145 |issue=2 |pages=289–325 |journal=The Journal of Physiology |doi=10.1113/jphysiol.1959.sp006143}}</ref> but are now known to be bidirectional in general.<ref name=":1">{{Cite book |title=Neuroscience |date=2001 |publisher=Sinauer Associates |isbn=978-0-87893-742-4 |editor-last=Purves |editor-first=Dale |edition=2nd |location=Sunderland, Mass |editor-last2=Williams |editor-first2=Stephen Mark}}</ref><ref name=":0">{{Cite book |title=Principles of neural science |date=2013 |publisher=McGraw-Hill medical |isbn=978-0-07-139011-8 |edition=5th |location=New York}}</ref> Later, it was found that chemicals could also be transported between cells through gap junctions.<ref>{{cite journal |pmid=5360587 |volume=166 |issue=3913 |title=Permeability and structure of junctional membranes at an electrotonic synapse |date=December 1969 |journal=Science |pages=1641–1643 |doi=10.1126/science.166.3913.1641 |last1=Payton |first1=B. W. |last2=Bennett |first2=M. V. L. |last3=Pappas |first3=G. D. |bibcode=1969Sci...166.1641P |s2cid=24701801}}</ref>

Implicit or explicit in most of the early studies is that the area of the gap junction was different in structure to the surrounding membranes in a way that made it look different. The gap junction had been shown to create a micro-environment between the two cells in the extracellular space or ''gap''. This portion of extracellular space was somewhat isolated from the surrounding space and also bridged by what we now call connexon pairs, which form even more tightly sealed bridges that cross the gap junction gap between two cells. When viewed in the plane of the membrane by freeze-fracture techniques, higher-resolution distribution of connexons within the gap junction plaque is possible.<ref>{{cite journal | pmid = 4935338 | doi=10.1083/jcb.47.1.49 | pmc=2108397 | volume=47 | issue=1 | title=An interpretation of liver cell membrane and junction structure based on observation of freeze-fracture replicas of both sides of the fracture |date=October 1970 | journal=J. Cell Biol. | pages=49–60 | last1 = Chalcroft | first1 = J. P. | last2 = Bullivant | first2 = S}}</ref>

Connexin free islands are observed in some junctions. The observation was largely without explanation until vesicles were shown by Peracchia using [[transmission electron microscopy]] (TEM) thin sections to be systematically associated with gap junction plaques.<ref>{{cite journal | pmid = 4120610 | pmc=2108965 | volume=57 | issue=1 | title=Low resistance junctions in crayfish. II. Structural details and further evidence for intercellular channels by freeze-fracture and negative staining |date=April 1973 | journal=J. Cell Biol. | pages=54–65 | last1 = Peracchia | first1 = C | doi = 10.1083/jcb.57.1.54}}</ref> Peracchia's study was probably also the first study to describe paired connexon structures, which he called a ''globule''. Studies showing vesicles associated with gap junctions and proposing the vesicle contents may move across the junction plaques between two cells were rare, as most studies focused on connexons rather than vesicles. A later study using a combination of microscopy techniques confirmed the early evidence of a probable function for gap junctions in intercellular vesicle transfer. Areas of vesicle transfer were associated with connexin free islands within gap junction plaques.<ref name ="Gruijters-vesicles"/> Connexin 43 has been shown to be necessary for the transfer of whole mitochondrias to neighboring cells, though whether the mitochondria is transferred directly through the membrane or within a vesicle has not been determined <ref>{{cite journal | last1 =Islam | first1 = M.| last2 = Das | first2 = S. |last3=Emin | first3=M. |display-authors= et al. | title=Mitochondrial transfer from bone-marrow–derived stromal cells to pulmonary alveoli protects against acute lung injury. | journal=Nat Med | volume=18 | pages=759–765 | year=2012 | issue = 5| doi=10.1038/nm.2736| pmid = 22504485| pmc = 3727429}}</ref>