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Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels

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  • Alexander V Maltsev
  • Victor A Maltsev
  • Michael D Stern

Abstract

Intracellular Local Ca releases (LCRs) from sarcoplasmic reticulum (SR) regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX) during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations) that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup) that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s). Background Ca (in locations lacking LCRs) quickly decays to resting Ca levels (

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  • Alexander V Maltsev & Victor A Maltsev & Michael D Stern, 2017. "Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release c," PLOS Computational Biology, Public Library of Science, vol. 13(8), pages 1-25, August.
    • Handle: RePEc:plo:pcbi00:1005675
    DOI: 10.1371/journal.pcbi.1005675
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    1. Alexander V Maltsev & Sean P Parsons & Mary S Kim & Kenta Tsutsui & Michael D Stern & Edward G Lakatta & Victor A Maltsev & Oliver Monfredi, 2017. "Computer algorithms for automated detection and analysis of local Ca2+ releases in spontaneously beating cardiac pacemaker cells," PLOS ONE, Public Library of Science, vol. 12(7), pages 1-21, July.
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