Novel Ca2+ dependence and time course of somatodendritic dopamine release: substantia nigra versus striatum - PubMed (original) (raw)

Novel Ca2+ dependence and time course of somatodendritic dopamine release: substantia nigra versus striatum

B T Chen et al. J Neurosci. 2001.

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 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.

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Figures

Fig. 1.

Evoked [DA]o in the presence of varying [Ca2+]o in striatum and SNc. Average evoked [DA]o during pulse-train stimulation (10 Hz, 30 pulses) in striatum (A) and SNc (B) in 0, 0.5, 1.5, 2.0, and 2.4 m

Ca2+. Maximum [DA]o in 1.5 m

was taken as 100%. In striatum, peak [DA]o was significantly increased by each step increase in [Ca2+]o(p < 0.001; 0 and 0.5 m

Ca2+; data from striatum were pooled). In SNc, significant increases were observed between 0 and 0.5 and 1.5 m

Ca2+ (p < 0.01); however, no additional increases were seen in 2.0 or 2.4 m

Ca2+. Data are means ± SEM (n = 6–17). The dashed lines_indicate 100%, and solid bars indicate the stimulation period. Note the difference in time scale between A and_B.

Fig. 2.

Ca2+ dependence of evoked DA release in striatum and SNc. Data were normalized such that 100% is the average maximum evoked [DA]o during pulse-train stimulation (3 sec, 10 Hz) in 1.5 m

Ca2+. In striatum, evoked [DA]oincreased progressively with increasing Ca2+ from 1.5 to 2.4 m

. In contrast, DA release was nearly half-maximal in nominally 0 m

Ca2+ in SNc but reached a plateau at 1.5 m

Ca2+. Data are means ± SEM (n = 6–17). **p < 0.01 and ***p < 0.001 indicates difference from the response in 1.5 m

Ca2+ for each region.

Fig. 3.

Time course of evoked [DA]o in striatum and SNc after single-pulse stimulation. A, Average evoked [DA]o by a single pulse (1 msec) in striatum (n = 8) and SNc (n = 9) (error bars have been omitted for clarity; see Fig. 4). The pattern of release differed significantly, as indicated by the difference in the time of maximum [DA]o(_t_max) and time to decay to 50% of maximum (_t_50) (p < 0.001 for both parameters; see Results for details). B, DA voltammograms recorded at the time of the maximum evoked [DA]o in striatum and SNc compared with a 1 μ

DA calibration voltammogram; these characteristic voltammograms confirm the identity of the released substance as DA (Rice et al., 1997; Chen et al., 2001).

Fig. 4.

Influence of DAT and D2 autoreceptor inhibition on evoked [DA]o in striatum and SNc after single-pulse stimulation. In the presence of GBR-12909 (GBR; 0.3 or 2 μ

) and sulpiride (sulp; 1 μ

), average maximum [DA]o evoked by a single pulse (1 msec) was significantly higher than in controls in striatum (A;p < 0.001 for both 0.3 and 2 μ

GBR-12909; n = 6–8) and SNc (B;p < 0.05 for pooled data from 0.3 and 2 μ

GBR-12909; n = 9) (see Results for details). Data are means ± SEM; the average maximum [DA]o in control conditions was taken as 100% for each region, indicated by the dashed lines.

Fig. 5.

Normalized evoked [DA]o curves indicate differences in time course between SNc versus striatum. Average [DA]o evoked by a single pulse in striatum (A) and SNc (B) in the presence and absence of GBR-12909 (GBR) plus sulpiride (sulp), with the maximum for each condition normalized to 100%. In striatum, both the _t_max and_t_50 of evoked [DA]o increased significantly in GBR-12909 in a concentration-dependent manner (p < 0.001 for each step compared with control; n = 6–8). Although the_t_50 in SNc was also increased compared with control (p < 0.01; n = 9 for pooled data from 0.3 and 2 μ

GBR-12909),_t_max was not altered (p > 0.05). C, When normalized curves for evoked [DA]o in SNc and striatum in maximally effective GBR-12909 plus sulpiride were superimposed on an expanded time scale, the overall time courses were similar (compare with Fig. 3A), with _t_50 values that did not differ significantly (p > 0.05). The time to reach maximum [DA]o,_t_max, however, remained significantly longer in the SNc (p < 0.01); dashed lines indicate _t_max for each region. Data are normalized means; error bars have been omitted for clarity (see Fig. 4).

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Novel Ca2+ dependence and time course of somatodendritic dopamine release: substantia nigra versus striatum - PubMed (original) (raw)