This input depends on the membrane 4-(Benzyloxy)phenol potential of the cones and the amount of feedback a cone receives. This last parameter depends on the horizontal cell membrane potential making it a closed loop system. The resting potential of horizontal cells is approximately 230 mV by virtue of a balance between a feedforward pathway and a feedback pathway. Blocking feedback leads to a shift of the Ca-current to positive potentials and thus to a reduction of glutamate release which will induce a hyperpolarization of horizontal cells. Therefore, blocking feedback without any other change in the system should lead to a reduction of the glutamate gated conductance in horizontal cells and thus hyperpolarization. Reports of the effect of HEPES on the membrane potential of horizontal cells are variable. Hirasawa and Kaneko and Davenport et al showed no change in horizontal cell membrane potential whereas Hare and Owen and Yamamoto at al showed a strong depolarization with HEPES, and Hanitzsch and Ku��ppers showed strong hyperpolarization. How to account for these differences? In addition to the feedforward and the feedback pathway, the membrane potential of horizontal cells will be determined by other conductances as well. These conductances will, at least, include potassium channels and hemichannels. These channels are potentially affected by changes in Tulathromycin B intracellular pH. Potassium channels can reduce their conductance upon intracellular acidification leading to an increase in depolarizing force on the membrane potential. Intracellular acidification leads also to the closure of hemichannels, which tend to depolarize horizontal cells. For the cone this will mean more glutamate release and for the horizontal cell this will mean a larger depolarizing drive. Since we are comparing the effect of HEPES on the horizontal cell membrane potential in various animal systems, the differences in results might be accounted for by different relative contributions of the various systems to the membrane potential. Finally, our experiments are performed in a condition where the GABAergic input to both horizontal cells and cones are blocked. Cones and horizontal cells in at least both fish and salamander have GABAA-receptors. Although GABA does not seem to be the major neurotransmitter that mediates the negative feedback signal to cones, changes in GABA will lead to changes in membrane conductance, membrane potential of cones and horizontal cells and in changes in receptive field size of horizontal cells. We cannot exclude that depolarization due to the application of HEPES or Tris seen by Yamamoto et al. is due to alterations in the GABAergic system. HEPES and acetate both lead to intracellular acidification and to a block of feedback. However, acetate does not whereas HEPES does lead to hyperpolarization of horizontal cells. How can we account for this difference? First it is important to recall that HEPES and acetate lead to changes in intracellular pH via very different mechanisms. Secondly we have to realize that HEPES in addition to intracellular acidification inhibits hemichannels directly which leads to hyperpolarization of horizontal cells. This hyperpolarizing effect is not present in the acetate experiments. In this paper we have shown that extracellular carbonic anhydrase is present in the outer and inner retina.