WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (38)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Piedras-Rentería, E. S.
Right arrow Articles by Tsien, R. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Piedras-Rentería, E. S.
Right arrow Articles by Tsien, R. W.

 Previous Article  |  Next Article 

The Journal of Neuroscience, December 1, 2001, 21(23):9185-9193

Increased Expression of alpha 1A Ca2+ Channel Currents Arising from Expanded Trinucleotide Repeats in Spinocerebellar Ataxia Type 6

Erika S. Piedras-Rentería1, Kei Watase2, 3, Nobutoshi Harata1, Olga Zhuchenko2, Huda Y. Zoghbi2, 3, Cheng Chi Lee2, and Richard W. Tsien1

1 Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, 2 Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, and 3 Howard Hughes Medical Institute, Houston, Texas 77030

The expansion of polyglutamine tracts encoded by CAG trinucleotide repeats is a common mutational mechanism in inherited neurodegenerative diseases. Spinocerebellar ataxia type 6 (SCA6), an autosomal dominant, progressive disease, arises from trinucleotide repeat expansions present in the coding region of CACNA1A (chromosome 19p13). This gene encodes alpha 1A, the principal subunit of P/Q-type Ca2+ channels, which are abundant in the CNS, particularly in cerebellar Purkinje and granule neurons. We assayed ion channel function by introduction of human alpha 1A cDNAs in human embryonic kidney 293 cells that stably coexpressed beta 1 and alpha 2delta subunits. Immunocytochemical analysis showed a rise in intracellular and surface expression of alpha 1A protein when CAG repeat lengths reached or exceeded the pathogenic range for SCA6. This gain at the protein level was not a consequence of changes in RNA stability, as indicated by Northern blot analysis. The electrophysiological behavior of alpha 1A subunits containing expanded (EXP) numbers of CAG repeats (23, 27, and 72) was compared against that of wild-type subunits (WT) (4 and 11 repeats) using standard whole-cell patch-clamp recording conditions. The EXP alpha 1A subunits yielded functional ion channels that supported inward Ca2+ channel currents, with a sharp increase in P/Q Ca2+ channel current density relative to WT. Our results showed that Ca2+ channels from SCA6 patients display near-normal biophysical properties but increased current density attributable to elevated protein expression at the cell surface.

Key words: P/Q-type calcium channel; alpha 1A; SCA6; polyglutamine; CAG repeats; cerebellar ataxia

Copyright © 2001 Society for Neuroscience  0270-6474/01/21239185-09$05.00/0


This article has been cited by other articles:


Home page
 J. Neurosci.Home page
J. Liu, T.-S. Tang, H. Tu, O. Nelson, E. Herndon, D. P. Huynh, S. M. Pulst, and I. Bezprozvanny
Deranged Calcium Signaling and Neurodegeneration in Spinocerebellar Ataxia Type 2
J. Neurosci., July 22, 2009; 29(29): 9148 - 9162.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Watase, C. F. Barrett, T. Miyazaki, T. Ishiguro, K. Ishikawa, Y. Hu, T. Unno, Y. Sun, S. Kasai, M. Watanabe, et al.
Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels
PNAS, August 19, 2008; 105(33): 11987 - 11992.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. Chen and E. S. Piedras-Renteria
Altered frequency-dependent inactivation and steady-state inactivation of polyglutamine-expanded {alpha}1A in SCA6
Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1078 - C1086.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S.-N. Yang and P.-O. Berggren
The Role of Voltage-Gated Calcium Channels in Pancreatic {beta}-Cell Physiology and Pathophysiology
Endocr. Rev., October 1, 2006; 27(6): 621 - 676.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. B. Kordasiewicz, R. M. Thompson, H. B. Clark, and C. M. Gomez
C-termini of P/Q-type Ca2+ channel {alpha}1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity
Hum. Mol. Genet., May 15, 2006; 15(10): 1587 - 1599.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
J. Wan, R. Khanna, M. Sandusky, D. M. Papazian, J. C. Jen, and R. W. Baloh
CACNA1A mutations causing episodic and progressive ataxia alter channel trafficking and kinetics
Neurology, June 28, 2005; 64(12): 2090 - 2097.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. F. Barrett, Y.-Q. Cao, and R. W. Tsien
Gating Deficiency in a Familial Hemiplegic Migraine Type 1 Mutant P/Q-type Calcium Channel
J. Biol. Chem., June 24, 2005; 280(25): 24064 - 24071.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
D. M. Kullmann
The neuronal channelopathies
Brain, June 1, 2002; 125(6): 1177 - 1195.
[Abstract] [Full Text] [PDF]


-
-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-