Ephaptic interactions within a chemical synapse: hemichannel-mediated ephaptic inhibition in the retina

The two best-known types of cell-cell communication are chemical synapses and electrical synapses, which are formed by gap junctions. A third, less well known, form of communication is ephaptic transmission, in which electric fields generated by a specific neuron alter the excitability of neighboring neurons as a result of their anatomical and electrical proximity. Ephaptic communication can be present in a variety of forms, each with their specific features and functional implications. One of these is ephaptic modulation within a chemical synapse. This type of communication has recently been proposed for the cone-horizontal cell synapse in the vertebrate retina. Evidence indicates that the extracellular potential in the synaptic terminal of photoreceptors is modulated by current flowing through connexin hemichannels at the tips of the horizontal cell dendrites, mediating negative feedback from horizontal cells to cones. This example can be added to the growing list of cases of ephaptic communication in the central nervous system.

[1]  S. Nawy,et al.  The gap junction blockers carbenoxolone and 18β-glycyrrhetinic acid antagonize cone-driven light responses in the mouse retina , 2003, Visual Neuroscience.

[2]  David L. Paul,et al.  Beyond the gap: functions of unpaired connexon channels , 2003, Nature Reviews Molecular Cell Biology.

[3]  John E. Dowling,et al.  Dopamine enhances excitatory amino acid-gated conductances in cultured retinal horizontal cells , 1987, Nature.

[4]  E. Furshpan,et al.  Two inhibitory mechanisms in the Mauthner neurons of goldfish. , 1963, Journal of neurophysiology.

[5]  E. Cherubini,et al.  Postsynaptic hyperpolarization increases the strength of AMPA-mediated synaptic transmission at large synapses between mossy fibers and CA3 pyramidal cells , 2000, Neuropharmacology.

[6]  C. Morgans,et al.  Localization and properties of voltage-gated calcium channels in cone photoreceptors of Tupaia belangeri , 1998, Visual Neuroscience.

[7]  J. L. Schnapf,et al.  Surround Antagonism in Macaque Cone Photoreceptors , 2003, Journal of Neuroscience.

[8]  S. Wu,et al.  Feedback connections and operation of the outer plexiform layer of the retina , 1992, Current Opinion in Neurobiology.

[9]  E. MacNichol,et al.  Inactivation of Horizontal Cells in Turtle Retina by Glutamate and Aspartate , 1972, Science.

[10]  Akimichi Kaneko,et al.  pH Changes in the Invaginating Synaptic Cleft Mediate Feedback from Horizontal Cells to Cone Photoreceptors by Modulating Ca2+ Channels , 2003, The Journal of general physiology.

[11]  M. Bennett,et al.  Rapid and Direct Effects of pH on Connexins Revealed by the Connexin46 Hemichannel Preparation , 1999, The Journal of general physiology.

[12]  S. Gasparini,et al.  Differences in amplitude–voltage relations between minimal and composite mossy fibre responses of rat CA3 hippocampal neurons support the existence of intrasynaptic ephaptic feedback in large synapses , 2000, Neuroscience.

[13]  E. A. Schwartz,et al.  Hemi‐gap‐junction channels in solitary horizontal cells of the catfish retina. , 1992, The Journal of physiology.

[14]  E. A. Schwartz,et al.  Transport-mediated synapses in the retina. , 2002, Physiological reviews.

[15]  H. Qian,et al.  Pharmacological enhancement of hemi-gap-junctional currents in Xenopus oocytes , 2002, Journal of Neuroscience Methods.

[16]  A. L. Byzov,et al.  Electrical feedback mechanism in the processing of signals in the outer plexiform layer of the retina , 1986, Vision Research.

[17]  P. Witkovsky,et al.  Sub-millimolar cobalt selectively inhibits the receptive field surround of retinal neurons , 1999, Visual Neuroscience.

[18]  D. Dacey,et al.  The Classical Receptive Field Surround of Primate Parasol Ganglion Cells Is Mediated Primarily by a Non-GABAergic Pathway , 2004, The Journal of Neuroscience.

[19]  S. DeVries,et al.  Exocytosed Protons Feedback to Suppress the Ca2+ Current in Mammalian Cone Photoreceptors , 2001, Neuron.

[20]  R. Köhling,et al.  Prolonged epileptiform bursting induced by 0-Mg2+ in rat hippocampal slices depends on gap junctional coupling , 2001, Neuroscience.

[21]  H. Spekreijse,et al.  Modulation of horizontal cell receptive fields in the light adapted goldfish retina , 1996, Vision Research.

[22]  W. Stell,et al.  Goldfish retina: functional polarization of cone horizontal cell dendrites and synapses , 1975, Science.

[23]  H Spekreijse,et al.  The feedback pathway from horizontal cells to cones A mini review with a look ahead , 1999, Vision Research.

[24]  H. Spekreijse,et al.  Horizontal cells feed back to cones by shifting the cone calcium-current activation range , 1996, Vision Research.

[25]  D. K. Patneau,et al.  Modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor desensitization by extracellular protons. , 2000, Molecular pharmacology.

[26]  S. Yazulla,et al.  Differential distribution of Shaker‐like and Shab‐like K+‐channel subunits in goldfish retina and retinal bipolar cells , 1998, The Journal of comparative neurology.

[27]  R. Dipolo,et al.  The effect of pH on Ca2+ extrusion mechanisms in dialyzed squid axons. , 1982, Biochimica et biophysica acta.

[28]  D. A. Burkhardt,et al.  Ionic influences on the prolonged depolarization of turtle cones in situ. , 1991, Journal of neurophysiology.

[29]  S. Barnes,et al.  Modulation of calcium-activated chloride current via pH-induced changes of calcium channel properties in cone photoreceptors , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  A. Keller,et al.  Ephaptic Interactions in the Mammalian Olfactory System , 2001, The Journal of Neuroscience.

[31]  M. Kamermans,et al.  Cobalt ions inhibit negative feedback in the outer retina by blocking hemichannels on horizontal cells , 2004, Visual Neuroscience.

[32]  M. Bennett,et al.  New roles for astrocytes: Gap junction hemichannels have something to communicate , 2003, Trends in Neurosciences.

[33]  H Spekreijse,et al.  The open- and closed-loop gain-characteristics of the cone/horizontal cell synapse in goldfish retina. , 2000, Journal of neurophysiology.

[34]  Liisa A. Tremere,et al.  Synaptic Activation of Presynaptic Glutamate Transporter Currents in Nerve Terminals , 2003, The Journal of Neuroscience.

[35]  R. Weiler,et al.  Molecular and Functional Diversity of Neural Connexins in the Retina , 2000, The Journal of Neuroscience.

[36]  Ruben Coronel,et al.  Conduction slowing by the gap junctional uncoupler carbenoxolone. , 2003, Cardiovascular research.

[37]  M Kamermans,et al.  Hemichannel-Mediated Inhibition in the Outer Retina , 2001, Science.

[38]  H. Ripps,et al.  pH regulation in horizontal cells of the skate retina. , 1998, Experimental eye research.

[39]  B. S. Winkler.  Buffer dependence of retinal glycolysis and ERG potentials. , 1986, Experimental eye research.

[40]  H. Qian,et al.  Evidence for hemi‐gap junctional channels in isolated horizontal cells of the skate retina , 1993, Journal of neuroscience research.

[41]  J. Dowling,et al.  Effects of acidic amino acid antagonists upon the spectral properties of carp horizontal cells: circuitry of the outer retina , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  A. Keller,et al.  Intercellular interactions in the mammalian olfactory nerve , 2003, The Journal of comparative neurology.

[43]  S. Mangel,et al.  Circadian Clock Regulation of pH in the Rabbit Retina , 2001, The Journal of Neuroscience.

[44]  GABAergic Modulation of Ephaptic Feedback in the Outer Retina , 2002 .

[45]  M. Chesler.  Regulation and modulation of pH in the brain. , 2003, Physiological reviews.

[46]  M. Volgushev,et al.  Neurophysiological analysis of long-term potentiation in mammalian brain , 1995, Behavioural Brain Research.

[47]  D. A. Burkhardt,et al.  Effects of synaptic blocking agents on the depolarizing responses of turtle cones evoked by surround illumination , 1990, Visual Neuroscience.

[48]  B. Hille,et al.  Ionic channels of the inner segment of tiger salamander cone photoreceptors , 1989, The Journal of general physiology.

[49]  B. Oakley,et al.  Extracellular pH in the isolated retina of the toad in darkness and during illumination. , 1989, The Journal of physiology.

[50]  J. Jefferys,et al.  Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions. , 1995, Physiological reviews.

[51]  H Korn,et al.  Electrical inhibition of Purkinje cells in the cerebellum of the rat. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[52]  E. Raviola,et al.  Intramembrane organization of specialized contacts in the outer plexiform layer of the retina. A freeze-fracture study in monkeys and rabbits , 1975, The Journal of cell biology.

[53]  S. Barnes,et al.  Carbenoxolone inhibition of voltage-gated Ca channels and synaptic transmission in the retina. , 2004, Journal of neurophysiology.

[54]  R. Weiler,et al.  Contribution of connexin26 to electrical feedback inhibition in the turtle retina , 2003, The Journal of comparative neurology.

[55]  M. Volgushev,et al.  Evidence for an ephaptic feedback in cortical synapses: postsynaptic hyperpolarization alters the number of response failures and quantal content , 1999, Neuroscience.

[56]  S. Barnes,et al.  Modulation of transmission gain by protons at the photoreceptor output synapse. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[57]  H Spekreijse,et al.  The dynamic characteristics of the feedback signal from horizontal cells to cones in the goldfish retina , 2001, The Journal of physiology.

[58]  R. Weiler,et al.  Identification and localization of connexin26 within the photoreceptor-horizontal cell synaptic complex , 2001, Visual Neuroscience.

[59]  M Kamermans,et al.  The involvement of glutamate-gated channels in negative feedback from horizontal cells to cones. , 2005, Progress in brain research.