Modeling short-term interval-force relations in cardiac muscle

J. Jeremy Rice, M. Saleet Jafri, Raimond L. Winslow

Research output: Contribution to journalArticlepeer-review

Abstract

This study employs two modeling approaches to investigate short-term interval-force relations. The first approach is to develop a low-order, discrete-time model of excitation-contraction coupling to determine which parameter combinations produce the degree of postextrasystolic potentiation seen experimentally. Potentiation is found to increase 1) for low recirculation fraction, 2) for high releasable fraction, i.e., the maximum fraction of Ca2+ released from the sarcoplasmic reticulum (SR) given full restitution, and 3) for strong negative feedback of the SR release on sarcolemmal Ca2+ influx. The second modeling approach is to develop a more detailed single ventricular cell model that simulates action potentials, Ca2+-handling mechanisms, and isometric force generation by the myofilaments. A slow transition from the adapted state of the ryanodine receptor produces a gradual recovery of the SR release and restitution behavior. For potentiation, a small extrasystolic release leaves more Ca2+ in the SR but also increases the SR loading by two mechanisms: 1) less Ca2+-induced inactivation of L-type channels and 2) reduction of action potential height by residual activation of the time-dependent delayed rectifier K+ current, which increases Ca2+ influx. The cooperativity of the myofilaments amplifies the relatively small changes in the Ca2+ transient amplitude to produce larger changes in isometric force. These findings suggest that short-term interval-force relations result mainly from the interplay of the ryanodine receptor adaptation and the SR Ca2+ loading, with additional contributions from membrane currents and myofilament activation.

Original languageEnglish (US)
Pages (from-to)H913-H931
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume278
Issue number3 47-3
DOIs
StatePublished - Mar 2000

Keywords

  • Calcium handling
  • Excitation-contraction coupling
  • Mechanical restitution

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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