Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

  1. Stephanie C Gantz
  2. Brooks G Robinson
  3. David C Buck
  4. James R Bunzow
  5. Rachael L Neve
  6. John T Williams
  7. Kim A Neve  Is a corresponding author
  1. Oregon Health & Science University, United States
  2. United States Department of Veterans Affairs, United States
  3. Massachusetts Institute of Technology, United States
7 figures

Figures

When virally expressed in midbrain dopamine neurons, D2S and D2L function as autoreceptors.

(A) Representative traces of whole-cell voltage clamp recordings, using a BAPTA-containing internal solution, of the outward current in D2S and D2L neurons induced by bath application of quinpirole …

https://doi.org/10.7554/eLife.09358.003
Weak intracellular calcium buffering reveals calcium-dependent desensitization of D2 autoreceptor-dependent GIRK currents in wild type dopamine neurons.

(A) Representative traces of whole-cell voltage clamp recordings of the outward current induced by bath application of quinpirole (10 μM) that was reversed by sulpiride (600 nM), using a BAPTA or …

https://doi.org/10.7554/eLife.09358.004
Figure 3 with 1 supplement
Increasing resting free internal calcium does not enhance desensitization of D2 autoreceptor-dependent GIRK currents.

(A) The amplitude of the quinpirole (10 μM)-induced current using BAPTA+Ca2+ internal solution was not different from the amplitudes using BAPTA or EGTA internal solutions (n = 7–15, ANOVA followed …

https://doi.org/10.7554/eLife.09358.005
Figure 3—figure supplement 1
The positive modulator of the SK channel, NS309, produces an outward current when using the BAPTA+Ca2+ internal solution.

(A) Representative trace of whole-cell voltage clamp recordings of the outward current induced by bath application of NS309 (10 μM), which was reversed by apamin (200 nM), using a BAPTA+Ca2+

https://doi.org/10.7554/eLife.09358.006
Figure 4 with 2 supplements
D2S but not D2L receptor-GIRK currents exhibit calcium-dependent desensitization.

(A) Representative traces of whole-cell voltage clamp recordings of the outward current in D2S and D2L neurons induced by bath application of quinpirole (30 μM) which was reversed by sulpiride (600 …

https://doi.org/10.7554/eLife.09358.007
Figure 4—figure supplement 1
Time course of desensitization of D2 receptor splice variant-GIRK currents.

(A) In D2S neurons, the decline in quinpirole (30 μM)-induced current was greater using EGTA internal compared to BAPTA (n = 10–16). (B) In D2L neurons, the decline in quinpirole-induced current …

https://doi.org/10.7554/eLife.09358.008
Figure 4—figure supplement 2
Expression and labeling of Flag-D2S receptors in dopamine neurons.

(A) Representative confocal microscopy images of Flag-D2S receptors clustered on the soma, dendrites, and spine-like structures of dopamine neurons, labeled by incubation of live slices in Alexa …

https://doi.org/10.7554/eLife.09358.009
Figure 5 with 1 supplement
Depleting intracellular calcium stores differentially modifies D2S and D2L receptor-dependent GIRK conductance.

(A) In wild type neurons, CPA (10 μM, > 20 min) reduced the decline in the quinpirole-induced current using EGTA internal and the effect was prevented with the use of BAPTA internal (n = 11–15, …

https://doi.org/10.7554/eLife.09358.010
Figure 5—figure supplement 1
Prolonged CPA application enhances D2 receptor-dependent currents produced by exogenous dopamine.

(A) Submaximal D2 receptor-dependent outward currents (I-DA) were produced once every 50 s by iontophoretic application of dopamine while recording with EGTA internal. Prolonged CPA (10 μM) …

https://doi.org/10.7554/eLife.09358.011
Figure 6 with 1 supplement
Blocking L-type calcium channels differentially modifies D2S and D2L receptor-dependent GIRK conductance.

(A, B) In wild type neurons, isradipine (300 nM, > 20 min) had no significant effect on the decline in quinpirole-induced (A) and baclofen-induced current (B) recorded with EGTA and BAPTA internal …

https://doi.org/10.7554/eLife.09358.012
Figure 6—figure supplement 1
Prolonged isradipine application enhances D2 receptor-dependent currents produced by exogenous dopamine.

(A) Submaximal D2 receptor-dependent outward currents (I-DA) were produced once every 50 s by iontophoretic application of dopamine while recording with EGTA internal. Prolonged isradipine (300 nM) …

https://doi.org/10.7554/eLife.09358.013
Effects of a single in vivo cocaine exposure on calcium-dependent D2 autoreceptor desensitization.

(A) In neurons from cocaine-treated wild type mice using EGTA internal, the quinpirole-induced current declined less compared to naïve/saline-treated mice, to a level comparable to the decline …

https://doi.org/10.7554/eLife.09358.014

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