A possible explanation could be that HEPES is a much faster buffer than bicarbonate even in the presence of carbonic anhydrase. This would mean that fast pH transients very close to the membrane, such as found by DeVries and Palmer et al., can occur in the synaptic cleft, but that sustained pH changes needed for a proton-mediated sustained feedback signal are fully buffered by bicarbonate. Our data support this Albaspidin-AA hypothesis. The feasibility of an ephaptic mechanism has been questioned. Dmitriev and Mangel concluded, based on a computational model, that the ephaptic interaction in the cone terminal is much too small to be of physiological relevance. We have scrutinized their assumptions and modified their model. Now it reproduces the essential features of the ephaptic feedback pathway and demonstrates that, under conditions of both full-field and annular illumination, the currents generated through the glutamate-gated channels and hemichannels of horizontal cells are sufficient to modulate the release of neurotransmitter from the terminals of cone photoreceptors. Moreover, for reasonable parameter values, this modulation can account for the measured negative feedback responses. In its present form, our model adds two essential features to the model developed by Dmitriev and Mangel, namely, the more widespread distribution of glutamate receptors and the non-linearity of the potassium channels on horizontal cells. Both have a major impact on the effectiveness of the feedback signals. The non-linearity of the potassium current has several major implications for the ephaptic mechanism, which were recognized earlier by Byzov and Shura-Bura. When horizontal cells start to hyperpolarize in response to the closure of their glutamate-gated channels, the potassium conductance will begin to activate. As a result, the horizontal cell will hyperpolarize to a greater extent than due solely to the closure of gGlu; this leads, in turn, to larger light-induced responses, and a concomitant increase in the feedback response. Moreover, the potassium conductance, which might limit the total current flowing through the hemichannels in depolarized conditions, increases with hyperpolarization allowing more current to flow through the hemichannels, and thus provides a further enhancement of ephaptic feedback. Dmitriev and Mangel suggest that ephaptic feedback should be positive for full-field stimulation because the reduction of the current flowing through the glutamate receptors will exceed the increase of the current through the hemichannels. This would indeed be the case if these two current sources were located at the same location, i.e. at the tips of the horizontal cell dendrites. However, with the addition of the potential dependence of the potassium channels and the more diffuse localization of the glutamate receptors, which more accurately reflects their distribution in situ, the present model predicts that ephaptic feedback will always be negative. In addition to the finding that these exposures cause cancer in different organs and significant mortality from cardiovascular and Orbifloxacin respiratory diseases, arsenic exposure has been associated with a number of developmental neurological disorders, peripheral neuropathies, and neuromuscular dysfunction. While neuropathies and some sensorimotor deficits have been attributed to high levels of arsenic impairing ATP generation and promoting necrosis.