Specific T-type calcium channel isoforms are associated with distinct burst phenotypes in deep cerebellar nuclear neurons

doi:10.1073/pnas.0601261103

Specific T-type calcium channel isoforms are associated with distinct burst phenotypes in deep cerebellar nuclear neurons

*Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada T2N 4N1; and
^†Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada V6T 1Z4

Communicated by William A. Catterall, University of Washington School of Medicine, Seattle, WA, February 15, 2006 (received for review January 12, 2006)

Abstract

T-type calcium channels are thought to transform neuronal output to a burst mode by generating low voltage-activated (LVA) calcium currents and rebound burst discharge. In this study we assess the expression pattern of the three different T-type channel isoforms (Ca_v3.1, Ca_v3.2, and Ca_v3.3) in cerebellar neurons and focus on their potential role in generating LVA spikes and rebound discharge in deep cerebellar nuclear (DCN) neurons. We detected expression of one or more Ca_v3 channel isoforms in a wide range of cerebellar neurons and selective expression of different isoforms in DCN cells. We further identify two classes of large-diameter DCN neurons that exhibit either a strong or weak capability for rebound discharge, despite the ability to generate LVA spikes when calcium currents are pharmacologically isolated. By correlating the Ca_v3 channel expression pattern with the electrophysiological profile of identified DCN cells, we show that Ca_v3.1 channels are expressed in isolation in DCN-burst cells, whereas Ca_v3.3 is expressed in DCN-weak burst cells. Ca_v3.1-expressing DCN cells correspond to excitatory or GABAergic neurons, whereas Ca_v3.3-expressing cells are non-GABAergic. The Ca_v3 class of LVA calcium channels is thus expressed in specific combinations in a wide range of cerebellar neurons but contributes to rebound burst discharge in only a select number of cell classes.

Footnotes

^‡To whom correspondence should be addressed. E-mail: rwturner{at}ucalgary.ca
Author contributions: M.L.M., J.E.M., W.H.M., and R.W.T. designed research; M.L.M., J.E.M., B.E.M., J.H., and R.R. performed research; T.P.S. and G.W.Z. contributed new reagents/analytic tools; M.L.M. and J.E.M. analyzed data; and M.L.M. and R.W.T. wrote the paper.
Conflict of interest statement: No conflicts declared.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF290212 –AF290214).
Abbreviations:

Abbreviations:

LVA,

low voltage-activated;

DCN,

deep cerebellar nuclear;

FI,

frequency current;

Ih,

hyperpolarization-activated current;

GAD,

glutamic acid decarboxylase.