Complex and rate-dependent beat-to-beat variations in Ca2+ transients of canine Purkinje cells

作者：Lee Young Seon; Dun Wen; Boyden Penelope A; Sobie Eric A^*

来源：Journal of Molecular and Cellular Cardiology, 2011, 50(4): 662-669.

DOI：10.1016/j.yjmcc.2010.12.023

• Ca2+ transients
• Pacing rate
• Conduction system
• Ca2+ sparks
• Ca2+ waves

Purkinje fibers play an essential role in transmitting electrical impulses through the heart, but they may also serve as triggers for arrhythmias linked to defective intracellular calcium (Ca2+) regulation. Although prior studies have extensively characterized spontaneous Ca2+ release in nondriven Purkinje cells, little attention has been paid to rate-dependent changes in Ca2+ transients. Therefore we explored the behaviors of Ca2+ transients at pacing rates ranging from 0.125 to 3 Hz in single canine Purkinje cells loaded with fluo3 and imaged with a confocal microscope. The experiments uncovered the following novel aspects of Ca2+ regulation in Purkinje cells: 1) the cells exhibit a negative Ca2+-frequency relationship (at 2.5 Hz, Ca2+ transient amplitude was 66 +/- 6% smaller than that at 0.125 Hz); 2) sarcoplasmic reticulum (SR) Ca2+ release occurs as a propagating wave at very low rates but is localized near the cell membrane at higher rates; 3) SR Ca2+ load declines modestly (10 +/- 5%) with an increase in pacing rate from 0.125 Hz to 2.5 Hz; 4) Ca2+ transients show considerable beat-to-beat variability, with greater variability occurring at higher pacing rates. Analysis of beat-to-beat variability suggests that it can be accounted for by stochastic triggering of local Ca2+ release events. Consistent with this hypothesis, an increase in triggering probability caused a decrease in the relative variability. These results offer new insight into how Ca2+ release is normally regulated in Purkinje cells and provide clues regarding how disruptions in this regulation may lead to deleterious consequences such as arrhythmias.

• 出版日期2011-4