The Journal of Neuroscience, May 10, 2006, ():
D2 Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity
J. Neurosci. Hahn et al.
26: 5240
Supplemental data
Files in this Data Supplement:
- supplemental material
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Supp. 1. Dynamic clamp shows that DA neuron spontaneous firing rate and regularity decrease in proportion to addition of virtual A-type K+ channels. A, Whole-cell current clamp recording from a cultured DA neuron before (control) and after addition of 200 or 300 nS of virtual A-type K+ channel conductance. Spontaneous firing activity was recorded without current injection. Broken lines indicate -40 mV. Plots of mean interspike interval (B) and the coefficient of variation of interspike interval (C) versus added virtual A-type channel conductance from the same DA neuron shown in A.
- supplemental material
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Supp. 2. Long-term regulation of DA neuron A-type channels and pacemaker activity. D2 receptors lower cAMP, which in turn results in a long-term decrease in A-type channel number. Hence, D2 antagonists induce upregulation of A-type channels. A-type channels produce a window current that reduces net inward pacemaker current. This makes pacemaker activity slower and more sensitive to noise from other channels.
- supplemental material
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Supp. 3. Comparison of short- and long-term regulation of DA neuron K+ channels by D2 receptors. Activation of D2 receptors directly triggers hyperpolarization by inducing opening of Girk channels. D2 receptors also inhibit adenylate cyclase to lower cAMP. cAMP inhibits A-type channel gating. Therefore, D2 receptor antagonists will tend to acutely close both Girk and A-type K+ channels and increase firing (i.e. antagonists such as haloperidol and sulpiride produce the opposite effect shown for the active D2 receptor). However, long-term treatment with antagonists increases the number of functional A-type channels.
