Desmosomes and the sodium channel complex: implications for arrhythmogenic
cardiomyopathy and Brugada syndrome
#MMPMID24656989
Cerrone M
; Delmar M
Trends Cardiovasc Med
2014[Jul]; 24
(5
): 184-90
PMID24656989
show ga
Mutations in proteins of the desmosome are associated with arrhythmogenic
cardiomyopathy (AC; also referred to as "ARVC" or "ARVD"). Life-threatening
ventricular arrhythmias often occur in the concealed phase of the disease before
the onset of structural changes. Among the various potential mechanisms for
arrhythmogenesis in AC, in this article, we concentrate on the relation between
desmosomes and sodium channel function. We review evidence indicating that (1)
loss of desmosomal integrity (including mutations or loss of expression of
plakophilin-2; PKP2) leads to reduced sodium current (INa), (2) the PKP2-INa
relation could be partly consequent to the fact that PKP2 facilitates proper
trafficking of proteins to the intercalated disc, and (3) PKP2 mutations can be
present in patients diagnosed with Brugada syndrome (BrS), thus supporting the
previously proposed notion that AC and BrS are not two completely separate
entities, but "bookends" in a continuum of variable sodium current deficiency and
structural disease.
|*Heart Rate/genetics
[MESH]
|Action Potentials
[MESH]
|Animals
[MESH]
|Arrhythmogenic Right Ventricular Dysplasia/genetics/*metabolism/physiopathology
[MESH]
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