Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the cardiac intercalated disc.
Circ Res
; 109(2): 193-201, 2011 Jul 08.
Article
en En
| MEDLINE
| ID: mdl-21617128
ABSTRACT
RATIONALE The early description of the intercalated disc defined 3 structures, all of them involved in cell-cell communication desmosomes, gap junctions, and adherens junctions. Current evidence demonstrates that molecules not involved in providing a physical continuum between cells also populate the intercalated disc. Key among them is the voltage-gated sodium channel complex. An important component of this complex is the cytoskeletal adaptor protein Ankyrin-G (AnkG). OBJECTIVE:
To test the hypothesis that AnkG partners with desmosome and gap junction molecules and exerts a functional effect on intercellular communication in the heart. METHODS ANDRESULTS:
We used a combination of microscopy, immunochemistry, patch-clamp, and optical mapping to assess the interactions between AnkG, Plakophilin-2, and Connexin43. Coimmunoprecipitation studies from rat heart lysate demonstrated associations between the 3 molecules. With the use of siRNA technology, we demonstrated that loss of AnkG expression caused significant changes in subcellular distribution and/or abundance of PKP2 and Connexin43 as well as a decrease in intercellular adhesion strength and electric coupling. Regulation of AnkG and of Na(v)1.5 by Plakophilin-2 was also demonstrated. Finally, optical mapping experiments in AnkG-silenced cells demonstrated a shift in the minimal frequency at which rate-dependence activation block was observed.CONCLUSIONS:
These experiments support the hypothesis that AnkG is a key functional component of the intercalated disc at the intersection of 3 complexes often considered independent the voltage-gated sodium channel, gap junctions, and the cardiac desmosome. Possible implications to the pathophysiology of inherited arrhythmias (such as arrhythmogenic right ventricular cardiomyopathy) are discussed.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Canales de Sodio
/
Ancirinas
/
Conexina 43
/
Placofilinas
/
Corazón
Límite:
Animals
Idioma:
En
Revista:
Circ Res
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos