Dopamine signaling is required for depolarization-induced slow current in cerebellar Purkinje cells.
Brief strong depolarization of cerebellar Purkinje cells produces a slow inward cation current. This current, called depolarization-induced slow current (DISC), is triggered by Ca influx in the Purkinje cell and is attenuated by a blocker of vesicular fusion. Previous work in other brain regions, such as the substantia nigra and ventral tegmental area, has shown that dopamine can be released from dendrites to produce paracrine and autocrine signaling. Here, we test the hypothesis that postsynaptic release of dopamine and autocrine activation of dopamine receptors is involved in DISC. Light immunohistochemistry showed that D(3) dopamine receptors, vesicular monoamine transporter type 2 (VMAT2), and dopamine plasma membrane transporters (DATs) were all expressed in cerebellar Purkinje cells. However, their expression was strongest in the gyrus region of cerebellar lobules IX and X. Comparison of DISC across lobules revealed that it was weak in the anterior portions of the cerebellum (lobules II, V, and VI) and strong in lobules IX and X. DISC was blocked by dopamine receptor antagonists (haloperidol, clozapine, eticlopride, and SCH23390). Likewise, DISC was strongly attenuated by inhibitors of VMAT (reserpine and tetrabenazine) and DAT (GBR12909 and rimcazole). These drugs did not produce DISC attenuation through blockade of depolarization-evoked Purkinje cell Ca transients. Purkinje cells in cerebellar slices derived from DAT-null mice expressed DISC, but this DISC ran down at a significantly higher rate than littermate controls. Together, these results suggest that strong Purkinje cell depolarization produces Ca-dependent release of vesicular postsynaptic dopamine that then excites Purkinje cells in an autocrine manner.
Kim
Yu Shin
YS
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Shin
Jung Hoon
JH
Hall
F Scott
FS
Linden
David J
DJ
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques / Q000379:methods; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D018756:GABA Antagonists; D011724:Pyridazines; D050637:Receptors, Dopamine D3; D050493:Vesicular Monoamine Transport Proteins; C049853:gabazine; D002118:Calcium; D004298:Dopamine