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Research ArticleNew Research, Neuronal Excitability

Cytosolic ATP Relieves Voltage-Dependent Inactivation of T-Type Calcium Channels and Facilitates Excitability of Neurons in the Rat Central Medial Thalamus

Tamara Timic Stamenic and Slobodan M. Todorovic
eNeuro 7 February 2018, 5 (1) ENEURO.0016-18.2018; https://doi.org/10.1523/ENEURO.0016-18.2018
Tamara Timic Stamenic
1Department of Anesthesiology, University of Colorado, Aurora, CO 80045
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Slobodan M. Todorovic
1Department of Anesthesiology, University of Colorado, Aurora, CO 80045
2Neuroscience Graduate Program, University of Colorado, Aurora, CO 80045
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Abstract

The central medial nucleus (CeM) is a part of the intralaminar thalamus, which is involved in the control of arousal and sensory processing. However, ionic conductances and mechanisms that regulate the activity of the CeM are not well studied. Here, we used in vitro electrophysiology in acute brain slices from adolescent rats to demonstrate that T-type calcium currents (T-currents) are prominent in the majority of the studied CeM neurons and are critical determinants of low-threshold calcium spikes (LTSs), which in turn regulate excitability of these neurons. Using an ATP-free internal solution decreased T-current density and induced a profound hyperpolarizing shift in steady-state inactivation curves while voltage-dependent activation kinetics were spared. Furthermore, selective pharmacological blockade of T-channels or use of an ATP-free solution reduced both tonic action potential (AP) frequency and rebound burst firing in CeM neurons. Our results indicate that T-channels are critical regulators of a thalamocortical circuit output and suggest that cytosolic ATP could be an endogenous regulatory mechanism in which T-channels may functionally gate sensory transmission and arousal in vivo.

  • ATP
  • calcium
  • low-voltage activated
  • thalamus

Footnotes

  • The authors declare no competing financial interests.

  • This work was supported in part by the National Institutes of Health Grant R01GM102525 (to S.M.T.).

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Cytosolic ATP Relieves Voltage-Dependent Inactivation of T-Type Calcium Channels and Facilitates Excitability of Neurons in the Rat Central Medial Thalamus
Tamara Timic Stamenic, Slobodan M. Todorovic
eNeuro 7 February 2018, 5 (1) ENEURO.0016-18.2018; DOI: 10.1523/ENEURO.0016-18.2018

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Cytosolic ATP Relieves Voltage-Dependent Inactivation of T-Type Calcium Channels and Facilitates Excitability of Neurons in the Rat Central Medial Thalamus
Tamara Timic Stamenic, Slobodan M. Todorovic
eNeuro 7 February 2018, 5 (1) ENEURO.0016-18.2018; DOI: 10.1523/ENEURO.0016-18.2018
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Keywords

  • ATP
  • calcium
  • low-voltage activated
  • thalamus

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