Here the authors show that PKP2 controls the expression of proteins involved in calcium cycling in adult mouse hearts, and that lack of PKP2 can cause arrhythmia in a structurally normal heart.
Dysfunctional desmosomes resulting in defective cell adhesion proteins, such as plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP-2), and desmoglein-2 (DSG-2) consequently cause loss of electrical coupling between cardiac myocytes, leading to myocyte cell death, fibrofatty replacement and arrhythmias.
Reduced connexin43 expression and localization to the intercalated disk occurs in heterozygous human PKP-2 mutations, potentially explaining the delayed conduction and propensity to develop arrhythmias seen in this disease.
The age at median cumulative symptom-free survival (32 versus 42 years) and at the median cumulative arrhythmia-free survival (34 versus 46 years) was lower among patients with a PKP2 mutation than among those without a PKP2 mutation (P<0.05).