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The Journal of Neuroscience, May 1, 1998, 18(9):3124-3137

Somatodendritic Depolarization-Activated Potassium Currents in Rat Neostriatal Cholinergic Interneurons Are Predominantly of the A Type and Attributable to Coexpression of Kv4.2 and Kv4.1 Subunits

W.-J. Song, T. Tkatch, G. Baranauskas, N. Ichinohe, S. T. Kitai, and D. J. Surmeier

Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis, Memphis, Tennessee 38163

Unlike other neostriatal neurons, cholinergic interneurons exhibit spontaneous, low-frequency, repetitive firing. To gain an understanding of the K+ channels regulating this behavior, acutely isolated adult rat cholinergic interneurons were studied using whole-cell voltage-clamp and single-cell reverse transcription-PCR techniques. Cholinergic interneurons were identified by the presence of choline acetyltransferase (ChAT) mRNA. Depolarization-activated potassium currents in cholinergic interneurons were dominated by a rapidly inactivating, K+-selective A current that became active at subthreshold potentials. Depolarizing prepulses inactivated this component of the current, leaving a delayed, rectifier-like current. Micromolar concentrations of Cd2+ dramatically shifted the voltage dependence of the A current without significantly affecting the delayed rectifier. The A-channel antagonist 4-aminopyridine (4-AP) produced a voltage-dependent block (IC50, ~1 mM) with a prominent crossover at millimolar concentrations. On the other hand, TEA preferentially blocked the sustained current component at concentrations <10 mM. Single-cell mRNA profiling of subunits known to give rise to rapidly inactivating K+ currents revealed the coexpression of Kv4.1, Kv4.2, and Kv1.4 mRNAs but low or undetectable levels of Kv4.3 and Kv3.4 mRNAs. Kv1.1, beta 1, and beta 2 subunit mRNAs, but not beta 3, were also commonly detected. The inactivation recovery kinetics of the A-type current were found to match those of Kv4.2 and 4.1 channels and not those of Kv1.4 or Kv1.1 and beta 1 channels. Immunocytochemical analysis confirmed the presence of Kv4.2 but not Kv1.4 subunits in the somatodendritic membrane of ChAT-immunoreactive neurons. These results argue that the depolarization-activated somatodendritic K+ currents in cholinergic interneurons are dominated by Kv4.2- and Kv4.1-containing channels. The properties of these channels are consistent with their playing a prominent role in governing the slow, repetitive discharge of interneurons seen in vivo.

Key words: A current; delayed rectifier; tetraethylammonium; 4-aminopyridine; voltage clamp; single-cell RT-PCR; acutely dissociated neurons; Kv1; Kv2; Kv3


Copyright © 1998 Society for Neuroscience  0270-6474/98/1893124-14$05.00/0


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J. Neurophysiol.Home page
J. Flores-Hernandez, S. Hernandez, G. L. Snyder, Z. Yan, A. A. Fienberg, S. J. Moss, P. Greengard, and D. J. Surmeier
D1 Dopamine Receptor Activation Reduces GABAA Receptor Currents in Neostriatal Neurons Through a PKA/DARPP-32/PP1 Signaling Cascade
J Neurophysiol, May 1, 2000; 83(5): 2996 - 3004.
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J. Neurosci.Home page
T. Tkatch, G. Baranauskas, and D. J. Surmeier
Kv4.2 mRNA Abundance and A-Type K+ Current Amplitude Are Linearly Related in Basal Ganglia and Basal Forebrain Neurons
J. Neurosci., January 15, 2000; 20(2): 579 - 588.
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J. Neurophysiol.Home page
W.-J. Song, T. Tkatch, and D. J. Surmeier
Adenosine Receptor Expression and Modulation of Ca2+ Channels in Rat Striatal Cholinergic Interneurons
J Neurophysiol, January 1, 2000; 83(1): 322 - 332.
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J. Neurophysiol.Home page
A. Bordey and H. Sontheimer
Differential Inhibition of Glial K+ Currents by 4-AP
J Neurophysiol, December 1, 1999; 82(6): 3476 - 3487.
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J. Neurophysiol.Home page
J.-M. Mienville, I. Maric, D. Maric, and J. R. Clay
Loss of IA Expression and Increased Excitability in Postnatal Rat Cajal-Retzius Cells
J Neurophysiol, September 1, 1999; 82(3): 1303 - 1310.
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J. Neurosci.Home page
P. G. Mermelstein, R. C. Foehring, T. Tkatch, W.-J. Song, G. Baranauskas, and D. J. Surmeier
Properties of Q-Type Calcium Channels in Neostriatal and Cortical Neurons are Correlated with beta Subunit Expression
J. Neurosci., September 1, 1999; 19(17): 7268 - 7277.
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J. Neurosci.Home page
G. Baranauskas, T. Tkatch, and D. J. Surmeier
Delayed Rectifier Currents in Rat Globus Pallidus Neurons Are Attributable to Kv2.1 and Kv3.1/3.2 K+ Channels
J. Neurosci., August 1, 1999; 19(15): 6394 - 6404.
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J. Neurophysiol.Home page
A. Pisani, P. Calabresi, D. Centonze, G. A. Marfia, and G. Bernardi
Electrophysiological Recordings and Calcium Measurements in Striatal Large Aspiny Interneurons in Response to Combined O2/Glucose Deprivation
J Neurophysiol, May 1, 1999; 81(5): 2508 - 2516.
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J. Neurophysiol.Home page
C. Pelz, J. Jander, H. Rosenboom, M. Hammer, and R. Menzel
IA in Kenyon Cells of the Mushroom Body of Honeybees Resembles Shaker Currents: Kinetics, Modulation by K+, and Simulation
J Neurophysiol, April 1, 1999; 81(4): 1749 - 1759.
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J. Neurosci.Home page
J. T. Blaine and A. B. Ribera
Heteromultimeric Potassium Channels Formed by Members of the Kv2 Subfamily
J. Neurosci., December 1, 1998; 18(23): 9585 - 9593.
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J. Neurosci.Home page
M. Martina, J. H. Schultz, H. Ehmke, H. Monyer, and P. Jonas
Functional and Molecular Differences between Voltage-Gated K+ Channels of Fast-Spiking Interneurons and Pyramidal Neurons of Rat Hippocampus
J. Neurosci., October 15, 1998; 18(20): 8111 - 8125.
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J. Neurosci.Home page
P. G. Mermelstein, W.-J. Song, T. Tkatch, Z. Yan, and D. J. Surmeier
Inwardly Rectifying Potassium (IRK) Currents Are Correlated with IRK Subunit Expression in Rat Nucleus Accumbens Medium Spiny Neurons
J. Neurosci., September 1, 1998; 18(17): 6650 - 6661.
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