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

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 Ca2+ channels, key elements in neurotrophin-promoted differentiation, to the total Ca2+ current in the CTG90 cells. Patch-clamp recordings showed that the relative proportion of pharmacologically isolated Ca2+ 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 Ca2+ channels in PC12 cells expressing the DM1 mutation. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.