Using autoradiographic and biochemical techniques, we studied the sodium-dependent forward and reverse transport of the neurotransmitter histamine in an arthropod photoreceptor in order to test whether the transporter plays a central role in visual signal transfer at this synapse. In particular, we asked whether the histamine transporter might be the important factor in synaptic adaptation, the process by which the operating range of the synapse adapts to increasing depolarizations of the photoreceptor in increasing background light. Drugs known from electrophysiological observations to interfere with synaptic adaptation blocked the uptake of [3H]histamine into photoreceptors. These drugs also blocked the sodium (Na)-triggered efflux of [3H]histamine, previously loaded into photoreceptors, via the histamine transporter. Several lines of evidence showed that efflux of [3H]histamine did not occur via calcium-dependent exocytosis. First, efflux occurred when the preparation was bathed in calcium (Ca)-free/EGTA salines or in cobalt (Co)-containing salines. Even more importantly, efflux could be elicited from axons, whose membranes must contain the transporter protein since they take up [3H]histamine independently from the presynaptic terminals. Since both adaptation and the histamine transporter are blocked by the same agents, the transporter may underlie adaptation by maintaining the cleft histamine concentration in a particular range independent of light intensity. We also characterized the transporter further and found that it is partially dependent on chloride ions, and that neither [3H]norepinephrine nor [3H]dopamine are transported (at 20 microM), adding to evidence that the transporter is highly selective for histamine.
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