Novel Ca2+ dependence and time course of somatodendritic dopamine release: substantia nigra versus striatum.
Somatodendritic release of dopamine (DA) in midbrain represents a novel form of intercellular signaling that inherently differs from classic axon-terminal release. Here we report marked differences in the Ca(2+) dependence and time course of stimulated increases in extracellular DA concentration ([DA](o)) between the substantia nigra pars compacta (SNc) and striatum. Evoked [DA](o) was monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry in brain slices. In striatum, pulse-train stimulation (10 Hz, 30 pulses) failed to evoke detectable [DA](o) in 0 or 0.5 mm Ca(2+) but elicited robust release in 1.5 mm Ca(2+). Release increased progressively in 2.0 and 2.4 mm Ca(2+). In sharp contrast, evoked [DA](o) in SNc was nearly half-maximal in 0 mm Ca(2+) and increased significantly in 0.5 mm Ca(2+). Surprisingly, somatodendritic release was maximal in 1.5 mm Ca(2+), with no change in 2.0 or 2.4 mm Ca(2+). Additionally, after single-pulse stimulation, evoked [DA](o) in striatum reached a maximum (t(max)) in <200 msec, whereas in SNc, [DA](o) continued to rise for 2-3 sec. Similarly, the time for [DA](o) to decay to 50% of maximum (t(50)) was 12-fold longer in SNc than striatum. A delayed t(max) in SNc compared with striatum persisted when DA uptake was inhibited by GBR-12909 and D(2) autoreceptors were blocked by sulpiride, although these agents eliminated the difference in t(50). Together, these data implicate different release mechanisms in striatum and SNc, with minimal Ca(2+) required to trigger prolonged DA release in SNc. Coupled with limited uptake, prolonged somatodendritic release would facilitate DA-mediated volume transmission in midbrain.
Chen
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Departments of Physiology and Neuroscience and Neurosurgery, New York University School of Medicine, New York, New York 10016, USA.
Rice
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D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011930:Reaction Time / Q000187:drug effects; D017448:Receptors, Dopamine D2; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D002352:Carrier Proteins; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D002118:Calcium; D004298:Dopamine