Acute atrial arrhythmogenesis in murine hearts following enhanced extracellular Ca2+ entry depends on intracellular Ca2+ stores

Aim To investigate the effect of increases in extracellular Ca2+ entry produced by the L-type Ca2+ channel agonist FPL-64176 (FPL) upon acute atrial arrhythmogenesis in intact Langendorff-perfused mouse hearts and its dependence upon diastolic Ca2+ release from sarcoplasmic reticular Ca2+ 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 μm) initially showed (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 μm) produced sustained and irregular patterns of cytosolic Ca2+ activity, independent of pacing. Nifedipine (0.5 μm), and caffeine (1.0 mm) and cyclopiazonic acid (CPA) (0.15 μm) pre-treatments respectively produced immediate and gradual reductions in the F/F0 peaks. Such nifedipine and caffeine, or CPA pre-treatments, abolished, or reduced, the effects of 0.1 and 1.0 μm FPL on cytosolic Ca2+ signals. FPL (1.0 μm) 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. Conclusion: Enhanced extracellular Ca2+ entry exerts acute atrial arrhythmogenic effects that is nevertheless dependent upon diastolic Ca2+ release. These findings complement reports that associate established, chronic, atrial arrhythmogenesis with decreased overall inward Ca2+ current

A High-resolution TOF Detector - A Possible Way to Compete with a RICH Detector

Using two identical 64-pixel Burle/Photonis MCP-PMTs to provide start and stop signals, they have achieved a timing resolution of {sigma}{sub Single{_}detector} {approx} 7.2 ps for N{sub pe} {approx} 50 photoelectrons (N{sub pe}) with a laser diode providing a 1 mm spot on the MCP window. The limiting resolution achieved was {sigma}{sub Single{_}detector} {approx} 5.0 ps for N{sub pe} {approx} 180, for which they estimate the MCP-PMT contribution of {sigma}{sub MCP-PMT} {approx} 4.5 ps. The electronics contribution is estimated as {sigma}{sub Electrons} = 3.42 ps. These results suggest that an ultra-high resolution TOF detector may become a reality at future experiments one day