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.