Link between desmosomes and sodium channel in ARVC

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Link between desmosomes and sodium channel in ARVC

Link between desmosomes and sodium channel in ARVC: Intercalated discs join the myocardial cells together. Desmosomes and adherens junctions in this region provide mechanical support to the junction. There are also gap junctions which allow transfer of metabolites and electrical impulses between the myocardial cells. Plakophilin-2 (PKP2) is a component of desmosomes and PKP2 mutations are seen in arrhythmogenic right ventricular cardiomyopathy (ARVC). NaV1.5 the major α subunit of the cardiac sodium channel also resides in the intercalated disc.

Priscila Y Sato, Hassan Musa, Wanda Coombs, Guadalupe Guerrero-Serna, Gustavo A Patiño, Steven M Taffet, Lori L Isom and Mario Delmar in a study [1] demonstrated that the loss of expression of PKP2 leads to decreased peak sodium current and delayed recovery from inactivation of the sodium channels. This leads to a substantial decrease in the sodium current and the conduction velocity. This in turn can lead to conduction block and re-entrant arrhythmias. This was an in-vitro study using neonatal rat myocytes.

Reference

  1. Priscila Y Sato, Hassan Musa, Wanda Coombs, Guadalupe Guerrero-Serna, Gustavo A Patiño, Steven M Taffet, Lori L Isom, Mario Delmar. Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes. Circ Res. 2009 Sep 11;105(6):523-6.