PubMed 15623702

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC1 , ClvC4

Title: Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current.

Authors: Jim Berg, Hong Jiang, Charles A Thornton, Stephen C Cannon

Journal, date & volume: Neurology, 2004 Dec 28 , 63, 2371-5

PubMed link:

Muscle fiber degeneration and myotonic discharges are the hallmarks of myotonic dystrophy (DM). The molecular basis for the myotonia was recently tied to abnormal splicing of the chloride channel (ClC-1) pre-mRNA, often resulting in UAG premature termination, which leads to decreased channel protein and therefore a reduced resting chloride conductance.The authors assessed the functional properties of two commonly occurring DM mRNA splice variants by expression in oocytes.Neither splice variant coded for a functional Cl- channel. Co-injection of alternative splice variants with wild-type ClC-1 cRNA reduced the current density and accelerated channel closure upon repolarization of the membrane.These data show that the aberrantly spliced chloride channel message exerts a dominant negative effect that may contribute to the development of myotonia.