Abstract
Cardiac Na channel remodeling provides a critical substrate for generation of reentrant arrhythmias in border zones of the infarcted canine heart. Recent studies show that Nav1.5 assembly and function are linked to ankyrin-G, gap, and mechanical junction proteins. In this study our objective is to expound the status of the cardiac Na channel, its interacting protein ankyrinG and the mechanical and gap junction proteins at two different times post infarction when arrhythmias are known to occur; that is, 48 hr and 5 day post coronary occlusion. Previous studies have shown the origins of arrhythmic events come from the subendocardial Purkinje and epicardial border zone. Our Purkinje cell (Pcell) voltage clamp study shows that INa and its kinetic parameters do not differ between Pcells from the subendocardium of the 48hr infarcted heart (IZPCs) and control non-infarcted Pcells (NZPCs). Immunostaining studies revealed that disturbances of Nav1.5 protein location with ankyrin-G are modest in 48 hr IZPCs. Therefore, Na current remodeling does not contribute to the abnormal conduction in the subendocardial border zone 48 hr post myocardial infarction as previously defined. In addition, immunohistochemical data show that Cx40/Cx43 co-localize at the intercalated disc (IDs) of control NZPCs but separate in IZPCs. At the same time, Purkinje cell desmoplakin and desmoglein2 immunostaining become diffuse while plakophilin2 and plakoglobin increase in abundance at IDs. In the epicardial border zone 5 days post myocardial infarction, immunoblot and immunocytochemical analyses showed that ankyrin-G protein expression is increased and re-localized to submembrane cell regions at a time when Nav1.5 function is decreased. Thus, Nav1.5 and ankyrin-G remodeling occur later after myocardial infarction compared to that of gap and mechanical junctional proteins. Gap and mechanical junctional proteins remodel in IZPCs early, perhaps to help maintain Nav1.5 subcellular location position and preserve its function soon after myocardial infarction.
Highlights
Impulse propagation in cardiac tissues depends on excitability of myocytes as well as electrical communication between myocytes
The abnormalities in the resting and action potentials (APs) of subendocardial Purkinje fibers surviving in the 24-48 hr infarcted heart persist even after they are enzymatically disaggregated and studied as single myocytes called IZPCs [10]
We report that average peak INa density of NZPCs did not differ from that of IZPCs and activation curves were similar in two cell types
Summary
Impulse propagation in cardiac tissues depends on excitability of myocytes as well as electrical communication between myocytes. Excitability of a single cell is determined by Nav1.5, the major cardiac Na channel α subunit, its proper cell placement and function. Altered Na+ current (INa) function in myocytes dispersed from the epicardial border zone (EBZ) of the 5 day infarcted canine heart plays an important role in the slowed conduction and subsequent reentry that occurs in this arrhythmic substrate [1,2,3]. What remains unknown are the changes in INa, Nav1.5 and its adapter protein ankyrin-G, in the arrhythmic Purkinje cells that survive in the subendocardial Border zone (IZPCs) [5]. We hypothesized that infarction induced remodeling of Nav1.5 is associated with changes in ankyrin-G in the canine epicardial and endocardial border zones
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
