Myotonic dystrophy CTG repeat expansion alters Ca2+channel functional expression in PC12 cells

Arturo Andrade, Mario Bermúdez de León, Oscar Hernández-Hernández, Bulmaro Cisneros, Ricardo Felix

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

We previously reported that expression of myotonic dystrophy (DM1) expanded CUG repeats impedes NGF-induced differentiation in a PC12 clone (CTG90 cells). Here, we present evidence for changes in the fractional contribution of distinct voltage-gated Ca 2+ channels, key elements in neurotrophin-promoted differentiation, to the total Ca 2+ current in the CTG90 cells. Patch-clamp recordings showed that the relative proportion of pharmacologically isolated Ca 2+ channel types differed between control and CTG90 cells. Particularly, the functional expression of N-type channels was significantly reduced. Though quantitative real-time RT-PCR revealed that transcripts for the pore-forming subunit encoding the N-type channels remained unchanged, the protein level analyzed by semi-quantitative Western blotting was down-regulated in the CTG90 cells. These data suggest modifications in the processing of N-type Ca 2+ channels in PC12 cells expressing the DM1 mutation.

Original languageEnglish
Pages (from-to)4430-4438
Number of pages9
JournalFEBS Letters
Volume581
Issue number23
DOIs
Publication statusPublished - 18 Sep 2007
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by Grants from Conacyt to R.F., and from the Muscular Dystrophy Association (MDA-3693) to B.C. Doctoral and postdoctoral fellowships from Conacyt to A.A. and O.H.H, respectively, are gratefully acknowledged. We also thank Victor Tapia for assistance with cell cultures, and Dr. Manuel Hernandez (Cinvestav-IPN, Mexico) for his generous gift of the β-actin antibodies.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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