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Effects of L-glutamate and its analogues on membrane potentials of solitary horizontal cells were studied by intracellular recording. L-glutamate depolarized these cells at micromolar concentrations (greater than or equal to 10 microM), while D-glutamate and L-alpha-amino adipic acid produced slight depolarizations only at millimolar concentrations. Neither L- nor D-aspartate, even at millimolar doses, produced any change in solitary horizontal-cell resting potential. Solitary horizontal-cell responses to L-glutamate did not desensitize detectably. Responses to pairs of brief, ionophoretic pulses of L-glutamate were nearly equal in amplitude at inter-pulse intervals as short as 50 ms. Responses to maintained applications of low doses of L-glutamate did not decline for as long as 2 min. Depolarizing responses were produced by ionophoretic applications of L-glutamate near cell somata as well as dendrites. The mean sensitivity was 1.4 +/- 1.5 mV/nC with a maximum of 5.1 mV/nC. Depolarizing responses to L-glutamate reversed in polarity at membrane potentials between 0 and -20 mV, were accompanied by a decrease in membrane slope resistance, and were suppressed by replacement of extracellular sodium ions with choline. These results demonstrate that chemosensitivity of retinal horizontal cells to acidic amino acids persists after dissociation protocols, and in several respects resembles that found in horizontal cells in situ. These findings are consistent with the notion that retinal horizontal cells receive a synaptic input involving L-glutamate or a similar substance.

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