Hemichannel-mediated inhibition in the outer retina

An essential feature of the first synapse in the retina is a negative feedb ack pathway from horizontal cells to cones. Here we show that at this synap se, connexin26 forms hemichannels on horizontal cell dendrites near the glu tamate release site of the cones. Blocking these hemichannels hyperpolarize s horizontal cells, modulates the Ca2+ channels of the cones, and abolishes all feedback-mediated responses. We propose a feedback mechanism in which the activity of the Ca2+ channels and the subsequent glutamate release of t he cones are modulated by a current through these hemichannels. Because the current through the hemichannels depends on the polarization of the horizo ntal cells, their activity modulates the output of the cones.