title: Myotonic dystrophy CTG repeat expansion alters Ca2+ channel functional expression in PC12 cells.
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.
authors: Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, Mexico.
authors: Arturo
authors: A
authors: Andrade
authors: Mario Bermúdez
authors: MB
authors: de León
authors: Oscar
authors: O
authors: Hernández-Hernández
authors: Bulmaro
authors: B
authors: Cisneros
authors: Ricardo
authors: R
authors: Felix
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D008858:Microscopy, Phase-Contrast; D009154:Mutation; D065636:Myotonin-Protein Kinase; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D019680:Trinucleotide Repeat Expansion / Q000235:genetics* / Q000502:physiology
chemical_list: C491911:Cacng2 protein, rat; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D012333:RNA, Messenger; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases; D009543:Nifedipine