Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes.
BACKGROUND
Plakophilin-2 (PKP2) is an essential component of the cardiac desmosome. Recent data show that it interacts with other molecules of the intercalated disc. Separate studies show preferential localization of the voltage-gated sodium channel (Na(V)1.5) to this region.


OBJECTIVE
To establish the association of PKP2 with sodium channels and its role on action potential propagation.


RESULTS
Biochemical, patch clamp, and optical mapping experiments demonstrate that PKP2 associates with Na(V)1.5, and that knockdown of PKP2 expression alters the properties of the sodium current, and the velocity of action potential propagation in cultured cardiomyocytes.


CONCLUSIONS
These results emphasize the importance of intermolecular interactions between proteins relevant to mechanical junctions, and those involved in electric synchrony. Possible relevance to the pathogenesis of arrhythmogenic right ventricular cardiomyopathy is discussed.
Sato
Priscila Y
PY
Center for Arrhythmia Research, University of Michigan, 5025 Venture Dr, Ann Arbor, MI 48108, USA.
Musa
Hassan
H
Coombs
Wanda
W
Guerrero-Serna
Guadalupe
G
Patiño
Gustavo A
GA
Taffet
Steven M
SM
Isom
Lori L
LL
Delmar
Mario
M
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000473:pathology; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology; D003896:Desmosomes / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D062554:NAV1.5 Voltage-Gated Sodium Channel; D051191:Plakophilins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D018754:Ventricular Dysfunction / Q000378:metabolism / Q000473:pathology
D062554:NAV1.5 Voltage-Gated Sodium Channel; D051191:Plakophilins; C568322:Scn5a protein, rat; D015222:Sodium Channels