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P. Chen, W. Yang, P. Wang, J. Luo, J. Zhao, X. Liu; Potential Contributions of pH-Sensitive PKDL Channels to the Feedback From Horizontal Cells to Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3282.
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Two potential mechanisms (i.e., chemical (pH) and electrical (ephaptic) feedbacks) from horizontal cells to photoreceptors have been proposed to sustain center-surround structure of retinal receptive field (Fahrenfort et al., PLoS 2009; Barnes, J Gen Physiol 2003). Despite extensive efforts in seeking experimental and theoretical evidence, neither of the two models has reached the stage to elucidate the present controversies. Our goals are set to reconcile apparent conflicts between the two major existing models.
We recently characterized the PKDL (polycystic kidney disease-like) channel complex for its potential role in acid sensing (Society of Neuroscience Abstract 2009). Data from electrophysiology and modeling support that PKDL is essentially activated by alkaline solutions and inhibited by acid solutions. PKDL might serve as the complementary sensor of known acid-sensing mechanisms, such as ASIC channels, to extend the range of pH sensing. Also, with its unique off-response upon removal of acid stimuli, PKDL could encode additional temporal information at the transduction level. A significant expression level of PKDL is evidenced in the retina (Basora et al., J Am Soc Nephrol 2002). The deletion of PKDL is likely responsible for retinal defects in Krd mice (Nomura et al., J Biol Chem 1998). We then incorporated the PKDL channels into the computer models (Liu et al., Ann Biomed Eng 2004) of photoreceptor-horizontal feedbacks, to investigate the potential roles of PKDL channels in photoreceptors and/or horizontal cells in the formation of center-surround receptive field.
PKDL, activated with pH increase, is able to serve as the base-sensor in the synaptic cleft. The change of PKDL conductance in photoreceptors could underlie the pH-dependent presynaptic release of photoreceptors. Moreover, the model with PKDL channels in horizontal cells also accommodates the ephaptic hypothesis because the overall current flow can be increased by way of PKDL channels, which are more active when proton concentration is lowered down upon light exposure.
Overall, a direct proton-monitoring mechanism, potentially mediated by PKDL, provides a novel model to help resolve the controversies in the feedback from horizontal cells to photoreceptors.
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