Channelpedia

PubMed 17923533


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav2.2



Title: Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy.

Authors: Sibylle Jablonka, Marcus Beck, Barbara Dorothea Lechner, Christine Mayer, Michael Sendtner

Journal, date & volume: J. Cell Biol., 2007 Oct 8 , 179, 139-49

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17923533


Abstract
Proximal spinal muscular atrophy (SMA) is a motoneuron disease for which there is currently no effective treatment. In animal models of SMA, spinal motoneurons exhibit reduced axon elongation and growth cone size. These defects correlate with reduced beta-actin messenger RNA and protein levels in distal axons. We show that survival motoneuron gene (Smn)-deficient motoneurons exhibit severe defects in clustering Cav2.2 channels in axonal growth cones. These defects also correlate with a reduced frequency of local Ca2+ transients. In contrast, global spontaneous excitability measured in cell bodies and proximal axons is not reduced. Stimulation of Smn production from the transgenic SMN2 gene by cyclic adenosine monophosphate restores Cav2.2 accumulation and excitability. This may lead to the development of new therapies for SMA that are not focused on enhancing motoneuron survival but instead investigate restoration of growth cone excitability and function.