Carol Beck, PhD
Philadelphia, PA 19107
(215) 503-3433 fax
Most Recent Peer-reviewed Publications
- Impaired autoproteolytic cleavage of mCLCA6, a murine integral membrane protein expressed in enterocytes, leads to cleavage at the plasma membrane instead of the endoplasmic reticulum
- Murine mCLCA5 is expressed in granular layer keratinocytes of stratified epithelia
- Inhibition of the A-type K+ channels of dorsal root ganglion neurons by the long-duration anesthetic butamben
- Molecular and functional analyses of two new calcium-activated chloride channel family members from mouse eye and intestine
- Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy
PhD, Vanderbilt University - 1993
BS, PharmD, University of Kentucky - 1983
Expertise and Research Interests
Mutations in the skeletal muscle chloride channel gene (CLCN-1) have been implicated in the human diseases myotonia congenita and recessive generalized myotonia and in animal models of myotonia in mouse, goat and dog. Myotonia is characterized by delayed relaxation of muscle secondary to sarcolemmal hyperexcitability and is the result of diminished chloride conductance in the muscle cell membrane. When chloride conductance (GCl) is reduced, either by drugs or dysfunctional channels, the repetitive myotonic contractions characteristic of the disease occur. These hereditary mutations are significant links between the pathology of these diseases and the basic physiology of skeletal muscle. We are using a combination of approaches to further our understanding of structure-function relationships of the affected voltage-gated ion channels and of the skeletal muscle diseases.
We want to understand how the molecular structure of ion channels contributes to their function. The carboxyl terminus of the ClC-1 chloride channel surrounding the mutation identified in myotonic goats contains multiple praline residues. Proline-rich domains have been found to participate in protein-protein interactions with specific binding motifs such as Src homology and WW domains. We hypothesize that the carboxyl terminus of ClC-1 participates in protein-protein interactions and that these interactions are important for proper channel function.
In other research in the laboratory, we have identified two murine members of the CLCA family (calcium-activated chloride channels), mCLCA5 and mCLCA6. We are examining the function of these proteins.