ACUTE ATRIAL ARRHYTHMOGENESIS IN MURINE HEARTS FOLLOWING ENHANCED EXTRACELLULAR CA ENTRY DEPENDS ON INTRACELLULAR CA STORES. Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] Journal article | | Title | ACUTE ATRIAL ARRHYTHMOGENESIS IN MURINE HEARTS FOLLOWING ENHANCED EXTRACELLULAR CA ENTRY DEPENDS ON INTRACELLULAR CA STORES. | | Author(s) | Zhang Y, Fraser JA, Schwiening C, Zhang Y, Killeen MJ, Grace AA, Huang CL | | Institution | Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, UK. | | Source | Acta Physiol (Oxf) 2009 Nov 3. | | Abstract | ABSTRACT
Aim: Investigation of 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.
Methods: Confocal microscope studies of Fluo-3 fluorescence in isolated atrial myocytes were performed in parallel with electrophysiological examination of Langendorff-perfused mouse hearts.
Results: Atrial myocytes stimulated at 1 Hz and exposed to FPL (0.1 muM) 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 muM) produced sustained and irregular patterns of cytosolic Ca(2+) activity, independent of pacing. Nifedipine (0.5 muM), and caffeine (1.0 mM) and cyclopiazonic acid (CPA) (0.15 muM) pretreatments respectively produced immediate, and gradual reductions in the F/F(0) peaks. Such nifedipine and caffeine, or CPA pretreatments, abolished, or reduced, the effects of 0.1 and 1.0 muM FPL on cytosolic Ca(2+) signals. FPL (1.0 muM) increased incidences 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.
Conclusion: Enhanced extracellular Ca(2+) entry exerts acute atrial arrhythmogenic effects nevertheless dependent upon diastolic Ca(2+) release. These findings complement reports that associate established, chronic, atrial arrhythmogenesis with decreased overall inward Ca(2+) current. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19886909 |
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