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. 2013 Sep 23;7:612. doi: 10.3389/fnhum.2013.00612

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Copyright © 2013 Vroman, Klaassen and Kamermans.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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(A) Ephaptic interactions will occur in every synapse. The strength of the ephaptic interaction will depend on the organization of the synapse. It will only become significant if the extracellular resistance is high enough. Left: synapse without significant ephaptic interaction. Middle and right: synapse with potentially significant ephaptic interactions. (B) Schematic drawing of the vertebrate outer retina. The photoreceptors are the light sensitive neurons in the retina (top layer). They are contacted by horizontal cells (HCs) (yellow) and bipolar cells (BCs) (black). The dendrites of both the HCs and the BCs invaginate the photoreceptor synaptic terminal. (C) Electron micrograph of a cone synaptic terminal. In this zebrafish HCs express Green Fluorescent Protein (GFP), which is visible as a black label in this image. Note that every ribbon is flanked by HC dendrites. R: synaptic ribbons. (Taken from: Klaassen et al., 2012) (D) Schematic drawing of the cone/HC synapse. In the dark, glutamate release is high and thus the glutamate receptors are activated (green resistors). A constant inward current flows through the connexin hemichannels (blue resistor) and because the resistance of the synaptic cleft is relatively high (white resistors), the synaptic space is slightly negative compared to the extrasynaptic space. When the retina receives a full field light stimulus, cones and consequently HCs hyperpolarize. This causes an increased inward current through the connexin hemichannels, resulting in an increased negativity of the synaptic cleft. The voltage sensitive Ca-channels on the cone (I_Ca, red circle) detect this as a slight depolarization of the membrane potential, effectively shifting the Ca-current activation potential towards more negative potentials (see Panel E). The influx of calcium increases and consequently the glutamate release. The current entering the HCs via the connexin hemichannels leaves the HCs via the potassium channel on the HC somata (orange resistor). (E) Feedback from HCs to cones modulates the Ca-current of cones. Ca-current of a cone in control condition (blue) and when HCs are hyperpolarized and feedback is active (yellow). (Modified from: Verweij et al., 1996).