Modulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons

D. James Surmeier; Jose Bargas; Hugh C. Hemmings; Angus C. Nairn; Paul Greengard

doi:10.1016/0896-6273(95)90294-5

Modulation of calcium currents by a D₁ dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons

D. James Surmeier^*, Jose Bargas, Hugh C. Hemmings, Angus C. Nairn, Paul Greengard

^*Corresponding author for this work

Neuroscience

Research output: Contribution to journal › Article › peer-review

486 Scopus citations

Abstract

In rat neostriatal neurons, D₁ dopamine receptors regulate the activity of cyclic AMP-dependent protein kinase (PKA) and protein phosphatase 1 (PP1). The influence of these signaling elements on high voltage-activated (HVA) calcium currents was studied using whole-cell voltage-clamp techniques. The application of D₁ agonists or cyclic AMP analogs reversibly reduced N- and P-type Ca²⁺ currents. Inhibition of PKA antagonized this modulation, as did inhibition of PP1, suggesting that the D₁ effect was mediated by a PKA enhancement of PP1 activity directed toward Ca²⁺ channels. In a subset of neurons, D₁ receptor-mediated activation of PKA enhanced L-type currents. The differential regulation of HVA currents by the D₁ pathway helps to explain the diversity of effects this pathway has on synaptic integration and plasticity in medium spiny neurons.

Original language	English (US)
Pages (from-to)	385-397
Number of pages	13
Journal	Neuron
Volume	14
Issue number	2
DOIs	https://doi.org/10.1016/0896-6273(95)90294-5
State	Published - Feb 1995

Funding

We would like to thank Dr. L. Dudkin for her technical help, A. Howe and P. Mermelstein for participating in some of the biophysical experiments, and Drs. B. Foehring, H. Kita, and R. Scroggs for critically reading the manuscript. This work was supported by USPHS grants NS 28889 and NS 26473 to D. J. S. and MH 40899 to P. G.

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1016/0896-6273(95)90294-5

Cite this

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title = "Modulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons",

abstract = "In rat neostriatal neurons, D1 dopamine receptors regulate the activity of cyclic AMP-dependent protein kinase (PKA) and protein phosphatase 1 (PP1). The influence of these signaling elements on high voltage-activated (HVA) calcium currents was studied using whole-cell voltage-clamp techniques. The application of D1 agonists or cyclic AMP analogs reversibly reduced N- and P-type Ca2+ currents. Inhibition of PKA antagonized this modulation, as did inhibition of PP1, suggesting that the D1 effect was mediated by a PKA enhancement of PP1 activity directed toward Ca2+ channels. In a subset of neurons, D1 receptor-mediated activation of PKA enhanced L-type currents. The differential regulation of HVA currents by the D1 pathway helps to explain the diversity of effects this pathway has on synaptic integration and plasticity in medium spiny neurons.",

author = "Surmeier, {D. James} and Jose Bargas and Hemmings, {Hugh C.} and Nairn, {Angus C.} and Paul Greengard",

note = "Funding Information: We would like to thank Dr. L. Dudkin for her technical help, A. Howe and P. Mermelstein for participating in some of the biophysical experiments, and Drs. B. Foehring, H. Kita, and R. Scroggs for critically reading the manuscript. This work was supported by USPHS grants NS 28889 and NS 26473 to D. J. S. and MH 40899 to P. G.",

year = "1995",

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doi = "10.1016/0896-6273(95)90294-5",

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AU - Surmeier, D. James

AU - Bargas, Jose

AU - Hemmings, Hugh C.

AU - Nairn, Angus C.

AU - Greengard, Paul

N1 - Funding Information: We would like to thank Dr. L. Dudkin for her technical help, A. Howe and P. Mermelstein for participating in some of the biophysical experiments, and Drs. B. Foehring, H. Kita, and R. Scroggs for critically reading the manuscript. This work was supported by USPHS grants NS 28889 and NS 26473 to D. J. S. and MH 40899 to P. G.

PY - 1995/2

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N2 - In rat neostriatal neurons, D1 dopamine receptors regulate the activity of cyclic AMP-dependent protein kinase (PKA) and protein phosphatase 1 (PP1). The influence of these signaling elements on high voltage-activated (HVA) calcium currents was studied using whole-cell voltage-clamp techniques. The application of D1 agonists or cyclic AMP analogs reversibly reduced N- and P-type Ca2+ currents. Inhibition of PKA antagonized this modulation, as did inhibition of PP1, suggesting that the D1 effect was mediated by a PKA enhancement of PP1 activity directed toward Ca2+ channels. In a subset of neurons, D1 receptor-mediated activation of PKA enhanced L-type currents. The differential regulation of HVA currents by the D1 pathway helps to explain the diversity of effects this pathway has on synaptic integration and plasticity in medium spiny neurons.

AB - In rat neostriatal neurons, D1 dopamine receptors regulate the activity of cyclic AMP-dependent protein kinase (PKA) and protein phosphatase 1 (PP1). The influence of these signaling elements on high voltage-activated (HVA) calcium currents was studied using whole-cell voltage-clamp techniques. The application of D1 agonists or cyclic AMP analogs reversibly reduced N- and P-type Ca2+ currents. Inhibition of PKA antagonized this modulation, as did inhibition of PP1, suggesting that the D1 effect was mediated by a PKA enhancement of PP1 activity directed toward Ca2+ channels. In a subset of neurons, D1 receptor-mediated activation of PKA enhanced L-type currents. The differential regulation of HVA currents by the D1 pathway helps to explain the diversity of effects this pathway has on synaptic integration and plasticity in medium spiny neurons.

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