استعرض مصدر Proton-mediated feedback inhibition of presynaptic calcium channels at the cone photoreceptor synapse

===HC membrane potential drives Ca signal modulation in presynaptic cones===

We showed that kainate and CNQX push the inhibitory feedback signal in opposing directions, presumably by shifting the presynaptic cone Ca channel activation curve in the positive or negative direction, respectively (Hirasawa and Kaneko, 2003). These drugs may achieve presynaptic modulation by acting on glutamate receptors found on dendrites of HCs that project into the synaptic invaginations of cone pedicles. The absence of AMPA or kainate receptor subunits on photoreceptors has been shown previously (Tachibana and Kaneko, 1988; Haverkamp et al., 2001a,b; Hirasawa and Kaneko, 2003), and we note that a Cl- conductance increase coupled to glutamate uptake (Sarantis et al., 1988; Arriza et al., 1997) is antagonized by kainate (Eliasof and Werblin, 1993; Eliasof et al., 1998). The lack of any detectable responses in the synaptic terminal layer of the zebrafish retina to the application of kainate in the present studies is consistent with the absence of AMPA receptors in photoreceptors. Kainate, by activating AMPA receptors, depolarizes HCs in the retinal slice. Because the imaging experiments are performed on light-adapted retinas, the HCs should be hyperpolarized and the depolarizing response is quite large. By depolarizing HCs, the feedback inhibition they send to the presynaptic cone Ca channels is enhanced. Conversely, CNQX antagonizes AMPA receptors, blocking the effects of glutamate released by the cones. This hyperpolarizes HCs further and reduces their inhibitory feedback to cone Ca channels. When revealed with a depolarizing (K+) stimulus, the calcium signal in the synaptic terminals was suppressed by kainate and enhanced by CNQX, providing evidence of modulation of the inhibitory feedback signal.