Figure 6.
Regulation of somatodendritic DA release by RyR-gated intracellular Ca2+ stores. a, Representative record of Fluo-5F fluorescence during RyR-activation by caffeine (5 mm), showing the time course of the resultant increase in [Ca2+]i in an SNc DAergic neuron. Recordings were made in nominally zero [Ca2+]o and in the presence of TTX (1 μm). b, Average [DA]o versus time profiles in the SNc evoked by local stimulation (30 pulses, 10 Hz) in the absence and presence of caffeine (Caff) (5 mm, n = 6). c, Summary of the effect of caffeine on peak [DA]o; control peak [DA]o (Con) was taken as 100%. Activation of RyRs by caffeine increased evoked [DA]o (n = 6, ***p < 0.001 vs control), implicating RyR-gated Ca2+ stores in somatodendritic DA release. d, Average [DA]o versus time profiles in SNc with caffeine (5 mm) after pretreatment with dantrolene (Dant) (10 μm), a RyR blocker (left, n = 8) or CPA (30 μm), a SERCA inhibitor (right, n = 6). e, Summary of the effect of caffeine in dantrolene or CPA on peak [DA]o; control peak [DA]o in either dantrolene or CPA alone was taken as 100%. Enhancement of evoked [DA]o by caffeine is prevented by pretreatment with dantrolene (n = 8, p > 0.05, Caff + Dant vs Dant alone) or CPA (n = 6, p > 0.05, Caff + CPA vs CPA alone), confirming the involvement of release of Ca2+ from RyR-gated stores in caffeine-mediated somatodendritic DA release. f, Average [DA]o versus time profiles in SNc in the absence and presence of dantrolene (10 μm) in 2.4 mm [Ca2+]o (left, n = 8) and 1.2 mm [Ca2+]o (right, n = 8). g, Summary of the effect of dantrolene on peak [DA]o; control peak [DA]o was taken as 100%. Although dantrolene had little effect on evoked [DA]o in 2.4 mm [Ca2+]o (n = 8, p > 0.05 vs control), a significant decrease in evoked [DA]o was revealed when dantrolene was applied in 1.2 mm [Ca2+]o (n = 8, **p < 0.01 vs control), implicating RyR activation in somatodendritic DA release.