Cobalt ions inhibit negative feedback in the outer retina by blocking hemichannels on horizontal cells

In goldfish, negative feedback from horizontal cells to cones shifts the activation function of the Ca(2+) current of the cones to more negative potentials. This shift increases the amount of Ca(2+) flowing into the cones, resulting in an increase in glutamate release. The increased glutamate release forms the basis of the feedback-mediated responses in second-order neurons, such as the surround-induced responses of bipolar cells and the spectral coding of horizontal cells. Low concentrations of Co(2+) block these feedback-mediated responses in turtle retina. The mechanism by which this is accomplished is unknown. We studied the effects of Co(2+) on the cone/horizontal network of goldfish retina and found that Co(2+) greatly reduced the feedback-mediated responses in both cones and horizontal cells in a GABA-independent way. The reduction of the feedback-mediated responses is accompanied by a small shift of the Ca(2+) current of the cones to positive potentials. We have previously shown that hemichannels on the tips of the horizontal cell dendrites are involved in the modulation of the Ca(2+) current in cones. Both the absence of this Co(2+)-induced shift of the Ca(2+) current in the absence of a hemichannel conductance and the sensitivity of Cx26 hemichannels to low concentrations of Co(2+) are consistent with a role for hemichannels in negative feedback from horizontal cells to cones.