FIG. 1.

Inhibition of Epac2 induces EAD-like [Ca²⁺] oscillations. (A) Typical confocal line-scan recording from a field-stimulated ARVM loaded with fluo-4 (upper), the associated line profile (middle), and selected Ca²⁺ transients on an expended timescale, both individually and normalized/superimposed (lower). Introduction of ESI-05 (25 μM) was followed by prolongation of the descending phase of the Ca²⁺ transient, which subsequently developed a distinct plateau phase with Ca²⁺ oscillations. s.p.: spontaneous SR Ca²⁺ release; black arrow: early prolongation of descending phase; red arrows: plateau/Ca²⁺ oscillations. ‘*’ indicates corresponding Ca²⁺ transient. (B) Cumulative data showing the percentage of cells exhibiting EAD-like Ca²⁺ oscillations following addition of ESI-05 (25 μM), ESI-05 + isoproterenol (ISO, 20 nM), ESI-05 + KN93 (10 μM), and ESI-05 + KN92 (10 μM). No cells exhibited EADs in the absence of ESI-05 (n = 30). (C) Original (left) and cumulative data (right) showing the effects of ESI-05 (25 μM) on the frequency of spontaneous Ca²⁺ sparks in ARVMs. **p < 0.01, n.s., not significant. ARVM, adult rat ventricular myocyte; EAD, early afterdepolarization arrhythmias; ISO, isoproterenol. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars