Electrical synapse
Electrical synapse
An electrical synapse, also called a gap junction, is an anatomically specialized junction between two nerve cells at which an electrical current flows directly from one cell into the other. It allows fast and reliable signal propagation between the neurons. After their discovery in 1959, electrical synapses have been considered to be present only in lower invertebrates or expressed transiently during development in the mammalians. Electrical synapses are present in many animal species and they are formed by connexin, innexin and pannexin proteins.
History of electrical synapse
In the second half of the nineteenth century there were two hypotheses for the organization of the nervous system. Proponents of the cell theory considered that the brain consisted of independent units, which we now call the neurons; while others thought of as a continuous web-like reticulum. Ramon y Cajal with Golgi staining method showed that the brain consisted of discrete units, neurons.
At the first decades of the twentieth century it was a debate on whether the transmission of information between neurons was chemical or electrical. After Otto Loewi's demonstration of chemical communication between neurons and heart muscle, the chemical synaptic transmission was seen as the only answer.
Thus, it was unexpected, when the electrical transmission was found. It was fist described in 1959 by Furshpan and Potter in the crayfish giant motor synapse and was involved in the animal’s escape reflex [1].
Later electrical transmission was found at a wide variety of synapses: in the leech sensory neurons [2], between motoneurons in the spinal cord of the frog [3], in the zebrafish retina [4]. In the mammalian brain electrical synapses were found in the inferion olive [5], locus coeruleus [6], hippocampus [7], retina [8], neocortex [9] and other parts of the brain.
Structure of the electrical synapse
At electrical synapse two neurons are separated by only 3.5 nm synaptic space [10]. The presynaptic and postsynaptic neurons are connected by the gap junction channels. The channels are composed of two hemi-channels called connexons. Connexons are formed of six subunits called connexins. Each connexin is a 7.5 nm long protein, having four membrane-spanning regions. Connexins may be identical or slightly different from one another [11]. More than 20 connexin genes have been found in the mouse and human genome.
The diameter of a gap junction channel is from 1.2 to 2.0 nm wide [11], which allows to pass molecules with molecular weight smaller or equal than 1 kD. The large diameter allows not only the flow of electric current, largely carried by potassium ions, but also exchange of small metabolites and intracellular signaling molecules thus making cytoplasmic continuity.
Properties of the electrical synapse
Electrical synapses usually transmit ions or molecules bidirectionally, equally well from either cell, differently from the chemical transmission. However, there are specialized gap junctions, which conduct the current in only one direction, from the presynaptic to the postsynaptic cell. These junctions are called rectifying synapses.
Most electrical synapses can transmit both depolarizing and hyperpolarizing current, but hyperpolarization spreads poorly. Indeed, when a current flows from a cell with a more positive charge, the cell becomes hyperpolarized, while the other one becomes depolarized. Thus the synapses can be characterized as synchronizing rather than excitatory or inhibitory.
Electrical synapses permit rapid signal transmission. Because of the absence of the synaptic delay, current spreads instantaneously from one cell to the next. Since the signal from cell to cell propagates passively, synaptic machinery is not needed and can’t be depleted, the electrical signaling is a reliable process.
Electrical synapses act as low-pass filters (preferentially transmitting low-frequency signals) as a consequence of a capacitance and conductance of the postsynaptic cell.
There is also evidence for plasticity at some of these synapses— that is, that the electrical connection they establish can strengthen or weaken as a result of activity.
Often electrical synapses are regulated developmentally, that is, they are expressed early during development, but later are eliminated.
Function of the electrical synapse
Gap junctions allow rapid signaling. The speed is important for certain escape reflexes and for signal processing.
Electrical transmission is also employed for connecting large groups of neurons. All the population of neurons is synchronized and its activity could be recorded as oscillatory waves in the brain. Thus small cells can act coordinately as one big cell. Moreover, the cell, which is electrically coupled, has a lower membrane resistance and requires a larger synaptic input to depolarize it. Once the depolarization is big enough, all network fires synchronously. This property is used when the response from all network needs to be all-or-none.
Besides these functions, electrical synapses transmit metabolic signals between the cells. Because of a large gap junction channel pore, calcium, ATP, cAMP, IP3 and other molecules can pass from one cell to the next. Gap junctions are also present between glia cells, allowing calcium waves and small metabolites propagation. There are certain neurological genetic diseases connected to gap junction malfunctions. Charcot-Marie-Tooth disease causes demyelination and results from mutations in one of the connexin genes expressed in the Schwann cells [10].
References
1. Furshpan, EE, Potter, DD. (1959). Transmission at the giant motor synapses of the crayfish. Journal of Physiology, 145: 289-325.
2. Baylor, DA, Nicholls, JG. (1969). Chemical and electrical synaptic connexions between cutaneous mechanoreceptor neurones in the central nervous system of the leech. J Physiol. 203(3):591-609.
3. Grinnell, AD. (1970). Electrical interaction between antidromically stimulated frog motoneurones and dorsal root afferents: enhancement by gallamine and TEA. J Physiol. 210(1):17-43. PMID: 5500776
4. McMahon, DG, Brown DR. (1994). Modulation of gap-junction channel gating at zebrafish retinal electrical synapses. J Neurophysiol. 72(5):2257-2268.
5. Llinas, R., Baker, R. and Sotelo, C., (1974). Electrotonic coupling between neurons in cat inferior olive. J. Neurophysiol. 37:560–571.
6. Christie, M.J., Williams, J.T. and North, R.A., (1989). Electrical coupling synchronizes subthreshold activity in locus coeruleus neurons in vitro from neonatal rats. J. Neurosci, 9:3584–3589.
7. MacVicar, BA, Dudek, FE. (1981). Electrotonic coupling between pyramidal cells: a direct demonstration in rat hippocampal slices. Science, 213(4509):782-785. PMID: 6266013.
8. DeVries, S.H., Qi, X., Smith, R., Makous, W. and Sterling, P., (2002). Electrical coupling between mammalian cones. Curr. Biol. 12:1900–1907.
9. Galarreta M, Hestrin S. (1999). A network of fast-spiking cells in the neocortex connected by electrical synapses. Nature, 402(6757):72-75. PMID: 10573418.
10. Kandel, ER, Schwartz, JH, Jessell, TM., (2000). Principles of Neural Science, 4th ed., McGraw-Hill, New York ISBN 0-8385-7701-6
11. Bennett MV, Zukin RS. (2004). Electrical coupling and neuronal synchronization in the mammalian brain. Neuron, 41(4):495-511. PMID 14980200