BACKGROUND: Triggered Purkinje ectopy can lead to the initiation of serious ventricular arrhythmias in post-myocardial infarction patients. In the canine model, Purkinje cells from the subendocardial border of the healing infarcted heart can initiate ventricular arrhythmias. Intracellular Ca(2+) abnormalities underlie these arrhythmias, yet the subcellular reasons for these abnormalities remain unknown. METHODS AND RESULTS: Using 2D confocal microscopy, we directly quantify and compare typical spontaneous Ca(2+) events in specific subcellular regions of normal Purkinje cells with those Purkinje cells from the subendocardium of the 48-hour infarcted canine heart (IZPCs). The Ca(2+) event rate was higher in the subsarcolemmal region of IZPCs when compared with normal Purkinje cells; IZPC amplitudes were higher, yet the spatial extents of these events were similar. The amplitude of caffeine-releasable Ca(2+) in either the subsarcolemmal or core regions of IZPCs did not differ from normal Purkinje cells, suggesting that Ca(2+) overload was not related to the frequency change. In permeabilized Purkinje cells from both groups, the event rate was related to free [Ca(2+)] in both subsarcolemmal and core, but in IZPCs, this event rate was significantly increased at each free Ca(2+), suggesting an enhanced sensitivity to Ca(2+) release. Furthermore, decays of wide long lasting Ca(2+) release events in IZPC's core were significantly accelerated compared with those in normal Purkinje cells. JTV519 (K201) suppressed IZPC cell wide Ca(2+) waves as well as normalized the enhanced event rate and its response to free Ca(2+). CONCLUSIONS: Increased spontaneous Ca(2+) release events in IZPCs are due to uniform regionally increased Ca(2+) release channel sensitivity to Ca(2+) without a change in sarcoplasmic reticulum content. In addition, Ca(2+) reuptake in IZPCs is accelerated. These properties would lower the threshold of Ca(2+) release channels, setting the stage for the highly frequent arrhythmogenic cell wide Ca(2+) waves observed in IZPCs.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)