J Physiol Physiology in Press
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Physiol Volume 586, Number 10, 2523-2538, May 15, 2008 DOI: 10.1113/jphysiol.2007.148197
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
586/10/2523    most recent
jphysiol.2007.148197v1
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Alviña, K.
Right arrow Articles by Khodakhah, K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alviña, K.
Right arrow Articles by Khodakhah, K.
Related Collections
Right arrow Neuroscience

NEUROSCIENCE

Selective regulation of spontaneous activity of neurons of the deep cerebellar nuclei by N-type calcium channels in juvenile rats

 Karina Alviña1,2 and Kamran Khodakhah1

1 Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2 Departmento de Ciencias Fisiológicas, Pontificia Universidad Católica de Chile, Santiago, Chile

The cerebellum coordinates movement and maintains body posture. The main output of the cerebellum is formed by three deep nuclei, which receive direct inhibitory inputs from cerebellar Purkinje cells, and excitatory collaterals from mossy and climbing fibres. Neurons of deep cerebellar nuclei (DCN) are spontaneously active, and disrupting their activity results in severe cerebellar ataxia. It is suggested that voltage-gated calcium channels make a significant contribution to the spontaneous activity of DCN neurons, although the exact identity of these channels is not known. We sought to delineate the functional role and identity of calcium channels that contribute to pacemaking in DCN neurons of juvenile rats. We found that in the majority of cells blockade of calcium currents results in avid high-frequency bursting, consistent with the notion that the net calcium-dependent current in DCN neurons is outward. We showed that the bursting seen in these neurons after block of calcium channels is the consequence of reduced activation of small-conductance calcium-activated (SK) potassium channels. With the use of selective pharmacological blockers we showed that L-, P/Q-, R- and T-type calcium channels do not contribute to the spontaneous activity of DCN neurons. In contrast, blockade of high-threshold N-type calcium channels increased the firing rate and caused the cells to burst. Our results thus suggest a selective coupling of N-type voltage-gated calcium channels with calcium-activated potassium channels in DCN neurons. In addition, we demonstrate the presence of a cadmium-sensitive calcium conductance coupled with SK channels, that is pharmacologically distinct from L-, N-, P/Q-, R- and T-type calcium channels.

(Received 13 November 2007; accepted after revision 25 March 2008; first published online 27 March 2008)
Corresponding author K. Khodakhah: Department of Neuroscience, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Kennedy Center, Room 506, Bronx, NY 10461, USA. Email: kkhodakh{at}aecom.yu.edu

This paper has online supplemental material.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 The Physiological Society.