Figure 7.

Arrhythmogenic Ca²⁺ waves and NCX activity in normal and HF atrial myocytes

A, protocol to monitor spontaneous Ca²⁺ wave activity. Cells were electrically paced (arrowheads) at 0.5 Hz in 7 mm extracellular [Ca²⁺] to enhance SR Ca²⁺ loading. Ca²⁺ waves were quantified during a 2-min rest period after cessation of pacing. The stars mark spontaneous Ca²⁺ waves without global cell-wide Ca²⁺ release and arrows mark arrhythmogenic Ca²⁺ waves. B, spontaneous Ca²⁺ wave in a single atrial myocyte observed during a rest period after pacing. The Ca²⁺ wave led to subsequent global Ca²⁺ release by triggering an AP and SR Ca²⁺ release typical for atrial ECC (‘arrhythmogenic Ca²⁺ wave’). C, confocal 2D image from a central focal plane revealing the ‘U-shaped’ wave front (left) and normalized fluorescence profiles (F/F₀) recorded along the dashed line (right). Da, frequency of spontaneous Ca²⁺ waves in normal and HF cells under control (CTRL) conditions (black), after the application of 2-APB (white) and SEA (grey). *P < 0.05 versus normal control; **P < 0.05 versus HF control, Student's t test. Db, latency of spontaneous Ca²⁺ waves. *P < 0.05, Student's t test. Dc, fraction of Ca²⁺ waves that induce a spontaneous AP and global CaTs (‘arrhythmogenic Ca²⁺ waves’) in HF atrial cells before (black) and after application of SEA (grey). In panel Dc square brackets indicate significant differences at P < 0.05, one-way ANOVA. Dd, absolute frequency of arrhythmogenic Ca²⁺ waves in normal and HF atrial myocytes in the absence and presence of SEA. To calculate absolute wave frequencies (panels a and d), also cells showing no waves were included. **P < 0.05 versus normal cells in the absence of SEA, Student's t test. *P < 0.05 versus control, Student's t test. Ea, protocol used to determine τ_CaT and τ_Caffeine for quantification of NCX activity. Eb, NCX activity in normal atrial cells (left), after inhibition of NCX in normal atrial cells with SEA, and in HF atrial cells. *P < 0.05 against normal cells, Student's t test.