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synapse. In this theory, hyperpolarization of the horizontal cell causes a hyperpolariza-
tion of the extracellular space around the cone synapse through leaky hemichannels in the
horizontal cell membrane [63]. The local hyperpolarization of the cone extracellular mem-
brane makes the voltage across the synaptic membrane appear more depolarized than the
rest of the cone membrane. This depolarization causes the voltage gated calcium channels
in the synapse to open more readily, causing more calcium flow into the cell. This theory
is supported by evidence Ofhemichannels in the synapse [63, 41]. More recently, however,
models of the resistivity of the extracellular fluid and analysis of the tightness of the con-
nections between horizontal cell and cone have demonstrated that the effect of such and
ephaptic synapse would likely be far too weak to cause any change in voltage across the cone
membrane [40].
A third theory for the feedback synapse advocated by several researchers involves pH
changes in the space around the synapse [ 104,28,55]. According to this theory, the horizon-
tal cell releases protons into the synaptic space in darkness. Hyperpolarizing the horizontal
cell causes a decrease in the proton release rate, causing an alkalinization of the synaptic
space. The alkalinization of the space interacts with the calcium channels, increasing the
current through them. One possibility for this activity is that the loss of positive charge in
the synaptic space with alkalinization causes an apparent depolarization of the membrane
across the voltage gated calcium channels, just as with the hemichannel feedback theory.
Evidence supporting the proton feedback theory is that changes in pH consistent with the
feedback show a corresponding change in the calcium current in goldfish cones [55]. Addi-