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Dopamine transporter–mediated conductances increase excitability of midbrain dopamine neurons

Nature Neuroscience volume 5, pages 971–978 (2002)Cite this article

Abstract

Uptake by Na+/Cl−-dependent neurotransmitter transporters is the principal mechanism by which extracellular biogenic amine concentrations are regulated. In addition to uptake, the cloned transporter proteins also elicit ion channel–like currents, but the physiological consequences of these currents are unknown. Here, whole-cell patch clamp and perforated-patch recordings show that substrates of the dopamine transporter (DAT), such as dopamine (DA) and amphetamine, increase the firing activity of rat DA neurons in culture. We found that these substrates elicit inward currents that are Na+-dependent and blocked by cocaine. These currents are primarily comprised of anions and result in an excitatory response in DA neurons at lower DA concentrations than are required for D2 autoreceptor activation. Thus, in addition to clearing extracellular DA, our results suggest that the currents associated with DAT modulate excitability and may regulate release of neurotransmitter from midbrain DA neurons.

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Figure 1: D2 receptor blockade reveals a stimulation of DA neurons.
Figure 2: DA and amphetamine elicit inward currents.
Figure 3: DAT-mediated currents and transport have a different concentration-dependence.
Figure 4: Substrate-mediated conductances are dependent on internal anions.
Figure 5: DAT-mediated conductance is an anion conductance.
Figure 6: Substrate-mediated anion conductance is depolarizing in gramicidin perforated-patch recordings.

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Acknowledgements

The authors wish to thank K. Poth, M. Sonders and M. Connor for helpful discussions and critical reading of the manuscript. This work was supported by DAO07595, Howard Hughes Medical Institute, and the National Alliance for Research on Schizophrenia and Depression (S.L.I. is an IRIS Project Investigator).

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  1. Vollum Institute and Howard Hughes Medical Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, 97201, Oregon, USA

    Susan L. Ingram, Balakrishna M. Prasad & Susan G. Amara

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Correspondence to Susan G. Amara.

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Ingram, S., Prasad, B. & Amara, S. Dopamine transporter–mediated conductances increase excitability of midbrain dopamine neurons. Nat Neurosci 5, 971–978 (2002). https://doi.org/10.1038/nn920

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