Electrical synapses, also known as gap junctions, were previously believed to have little significance in the functioning of the adult mammalian central nervous system (CNS), despite being known to exist for a long time. However, recent findings have shown that these synapses are actually quite common and may play a crucial role in neuronal functions.

An electrical synapse acts as a pathway of low resistance between cells, allowing the direct flow of current from one cell to another. It also facilitates the exchange of small molecules between cells. These synapses can be found in the CNS of various animals, ranging from invertebrates to mammals. They are present not only between neurons but also between glial cells. Neuronal electrical coupling has been observed in numerous brain regions, including the cerebellum, spinal cord, neocortex, thalamus, hippocampus, olfactory bulb, retina, and striatum.

A gap junction serves as the physical structure of an electrical synapse. It appears as plaque-like structures where the plasma membranes of the connected cells come into close proximity, narrowing the intercellular space to approximately 3 nm. These spaces are filled with electron-dense material. Freeze-fracture electron micrographs of gap junctions reveal regular arrays of intramembrane particles that correspond to the proteins forming the intercellular channels connecting the cells. These channels have a relatively large diameter of 1 to 2 nm, allowing the permeation of ions and small molecules up to around 1 kDa in size.

The structure of a gap junction is illustrated in Figure 6.1. The schematic view shows the narrowing of the intercellular space to 3.5 nm at the junction, where multiple channels are present. Each channel is formed by two connexon hemichannels, and each connexon consists of six connexin subunits. An electron micrograph showcases a complex synaptic arrangement called a glomerulus found in the inferior olive and some other CNS regions. In this image, two dendritic spines are coupled by a gap junction. An axon terminal filled with synaptic vesicles can be seen in the upper right part of the panel. The electron-dense material marking the active zones is indicated by large arrowheads, while black dots represent immunogold labeling for GABA, identifying this terminal as GABAergic. Red arrowheads point to synaptic vesicles.

Each gap junction channel is formed by two hemichannels (connexons), contributed by each cell. Each connexon is composed of six connexin protein subunits, encoded by a gene family consisting of at least 21 different members in mammals. Another protein family known as pannexins has also been identified in the formation of gap junctions. Gap junctions formed by different connexins possess distinct biophysical properties (gating and conductance) and cellular distributions. While the CNS expresses at least 10 types of connexins, connexin36 is the major neuronal connexin in the adult CNS. Other connexin types found in the CNS form gap junctions between glial cells or are primarily expressed transiently during development.
Although their existence in the mammalian central nervous system (CNS) has been known for a long time, electrical synapses, or gap junctions, between neurons were thought to be of relatively little importance for the functioning of the adult mammalian CNS. Only recently has it become apparent that these synapses are quite common and that they may underlie important neuronal functions.
An electrical synapse is effectively a low-resistance pathway between cells that allows current to flow directly from one cell to another and, more generally, allows the exchange of small molecules between cells. Electrical synapses are present in the CNS of animals from invertebrates to mammals. They are present between glial cells as well as between neurons. Electrical coupling of neurons has been demonstrated for most brain regions, including the inferior olive, cerebellum, spinal cord, neocortex, thalamus, hippocampus, olfactory bulb, retina, and striatum.
A gap junction is the morphological correlate of an electrical synapse (see also ). These junctions are plaque-like structures in which the plasma membranes of the coupled cells become closely apposed (the intercellular space narrows to ≈ 3 nm) and filled with electron-dense material (Fig. 6.1 ). Freeze-fracture electron micrographs of gap junctions display regular arrays of intramembrane particles that correspond to proteins that form the intercellular channels connecting the cells. The typical channel diameter is large (1 to 2 nm), thus making it permeable not only to ions but also other small molecules up to approximately 1 kDa in size.
.28 µm • Fig. 6.1 Gap junction structure. A, Schematic view of the gap junction showing narrowing of the intercellularspaceto3.5nmatthejunction.Thegapjunctionhasmultiplechannels,witheachchannel formed by two connexon hemichannels. Each connexon in turn comprises six connexin subunits. B,Electronmicrographofpartofacomplexsynapticarrangementcalledaglomerulusthatisfoundin theinferioroliveandsomeotherCNSregions.Twodendriticspinesarecoupledbyagapjunction(small black arrows).Anaxonterminalpackedwithsynapticvesiclesfillstheupperrightpartofthepanel.Large arrowheadspointtotheelectron-densematerialthatmarkstheactivezones.Blackdotsareimmunogold labelingforGABA,thusidentifyingthisterminalasGABAergic.Redarrowheadspointtosynapticvesicles. (FromDeZeeuwCIetal.J Neurosci1996;16:3420.Copyright1996bytheSocietyforNeuroscience.)
Eachgapjunctionchannelisformedbytwohemichannels(calledconnexons),onecontributedbyeachcell.Eachconnexon,inturn,isahexamerofconnexinproteinsubunits,whichareencodedforbyagenefamilyofatleast21differentmembersinmammals.(Asecondfamilyofproteinsthatformgapjunctions,thepannexins,hasalsobeenidentified.)Gapjunctionsformedbydifferentconnexinshavedistinctbiophysicalproperties(gatingandconductance)andcellulardistributions.Althoughatleast10connexintypesareexpressedintheCNS,connexin36(connexinsarenamedaccordingtotheirmolecularweight;thus,thenumberreferstotheapproximatemolecularweightoftheconnexininkilodaltons)isthemajorneuronalconnexinintheadultCNS.OtherconnexintypesfoundintheCNSformgapjunctionsbetweenglialcellsorareprimarilyexpressedtransientlyduringdevelopment.