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K.E. Gavrikov, A.V. Dmitriev, K.T. Keyser, S.C. Mangel; Chloride Cotransporters Mediate Direction Selectivity of Starburst Amacrine Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4132.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Recent evidence indicates that directionally-selective responses occur first in the retina in the dendrites of starburst amacrine cells, interneurons presynaptic to directionally-selective ganglion cells. Because blockade of the Na-K-Cl and K-Cl cotransporters eliminates the directional responses of directionally-selective ganglion cells (Mangel et al., 2001, 2002, ARVO), we studied whether the chloride cotransporters mediate the directional responses of starburst amacrine cells. Methods: Extracellular and intracellular recordings of DAPI-stained rabbit displaced starburst amacrine cells were obtained and the effects of blocking the chloride cotransporters assessed. The identity of starburst amacrine cells was confirmed with Neurobiotin injections. Results: We report that starburst amacrine cells depolarize and generate action potentials to stimuli that move from their somata to the periphery, but not to stimuli that move from the periphery to their somata. Moreover, the directional responses of starburst cell dendrites are highly sensitive to the polarity of their chloride gradients. Reducing the transmembrane chloride gradient by ion substitution or by blocking the K-Cl cotransporter with furosemide (25 mM) results in the starburst cells responding equally to light moving in opposite directions. Conversely, increasing the chloride gradient by blocking the Na-K-Cl cotransporter with bumetanide (10 mM) eliminates responses to light moving in either direction although the starburst cells still respond to stationary, flashing stimuli. Conclusions: These results indicate that the Na-K-Cl and K-Cl cotransporters play a key role in the generation of direction selectivity and suggest that the asymmetric distribution of the two cotransporters along starburst amacrine cell dendrites mediates direction selectivity.
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