Novel Ca2+Dependence and Time Course of Somatodendritic Dopamine Release: Substantia Nigra versus Striatum

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Abstract
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 Ca2+ 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 mmCa2+ but elicited robust release in 1.5 mm Ca2+. Release increased progressively in 2.0 and 2.4 mm Ca2+. In sharp contrast, evoked [DA]o in SNc was nearly half-maximal in 0 mm Ca2+ and increased significantly in 0.5 mm Ca2+. Surprisingly, somatodendritic release was maximal in 1.5 mmCa2+, with no change in 2.0 or 2.4 mmCa2+. Additionally, after single-pulse stimulation, evoked [DA]o in striatum reached a maximum (tmax) in o continued to rise for 2–3 sec. Similarly, the time for [DA]o to decay to 50% of maximum (t50) was 12-fold longer in SNc than striatum. A delayed tmax in SNc compared with striatum persisted when DA uptake was inhibited by GBR-12909 and D2 autoreceptors were blocked by sulpiride, although these agents eliminated the difference in t50. Together, these data implicate different release mechanisms in striatum and SNc, with minimal Ca2+ required to trigger prolonged DA release in SNc. Coupled with limited uptake, prolonged somatodendritic release would facilitate DA-mediated volume transmission in midbrain.