Acute atrial arrhythmogenesis in murine hearts following enhanced extracellular Ca(2+) entry depends on intracellular Ca(2+) stores.

To investigate the effect of increases in extracellular Ca(2+) entry produced by the L-type Ca(2+) channel agonist FPL-64176 (FPL) upon acute atrial arrhythmogenesis in intact Langendorff-perfused mouse hearts and its dependence upon diastolic Ca(2+) release from sarcoplasmic reticular Ca(2+) stores. Confocal microscope studies of Fluo-3 fluorescence in isolated atrial myocytes were performed in parallel with electrophysiological examination of Langendorff-perfused mouse hearts. Atrial myocytes stimulated at 1 Hz and exposed to FPL (0.1 microm) initially showed (<10 min) frequent, often multiple, diastolic peaks following the evoked Ca(2+) transients whose amplitudes remained close to control values. With continued pacing (>10 min) this reverted to a regular pattern of evoked transients with increased amplitudes but in which diastolic peaks were absent. Higher FPL concentrations (1.0 microm) produced sustained and irregular patterns of cytosolic Ca(2+) activity, independent of pacing. Nifedipine (0.5 microm), and caffeine (1.0 mm) and cyclopiazonic acid (CPA) (0.15 microm) pre-treatments respectively produced immediate and gradual reductions in the F/F(0) peaks. Such nifedipine and caffeine, or CPA pre-treatments, abolished, or reduced, the effects of 0.1 and 1.0 microm FPL on cytosolic Ca(2+) signals. FPL (1.0 microm) increased the incidence of atrial tachycardia and fibrillation in intact Langendorff-perfused hearts without altering atrial effective refractory periods. These effects were inhibited by nifedipine and caffeine, and reduced by CPA. Enhanced extracellular Ca(2+) entry exerts acute atrial arrhythmogenic effects that is nevertheless dependent upon diastolic Ca(2+) release. These findings complement reports that associate established, chronic, atrial arrhythmogenesis with decreased overall inward Ca(2+) current.