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Spontaneous sarcoplasmic reticulum Ca2+ release leads to heterogeneity of contractile and electrical properties of the heart

  • E. G. Lakatta
  • A. Talo
  • M. C. Capogrossi
  • H. A. Spurgeon
  • M. D. Stern

Summary

The cytosolic Ca2+ (Cai) oscillation generated by the sarcoplasmic reticulum (SR) in response to an action potential (AP) occurs relatively synchronously within and among cells. The SR can also generate spontaneous Cai oscillations (S-CaOs), i.e., not triggered by sarcolemmal depolarization. The local increase in Cai due to S-CaOs is equivalent to that induced by an AP. Heterogeneity of diastolic Cai caused by asynchronous S-CaOs among cells within myocardial tissue leads to heterogeneous myofilament activation, the summation of which produces a Ca2+-dependent component to diastolic tone. The local increases in Cai due to S-CaOs also cause oscillatory sarcolemmal depolarizations due to Ca2+ modulation of the Na/Ca exchanger and of non-specific cation channels. Thus, inhomogeneous levels of diastolic Cai may lead to heterogeneity in cell coupling and thus may also affect the impulse conduction. The magnitude of the S-CaOs induced diastolic tonus and membrane depolarization varies with the extent to which S-CaOs are synchronized; partially synchronized S-CaOs following an AP induced SR Ca2+ release produce an aftercontraction and after depolarization. When local S-CaOs is sufficiently synchronized within the cell the resultant depolarization summates and can be sufficient to trigger spontaneous AP.

Inhomogeneity of diastolic SR Ca2+ loading and sarcomere lengths within individual cardiac cells due to S-CaOs leads to inhomogeneous systolic Cai levels and sarcomere length inhomogeneities in response a subsequent AP; this heterogeneity compromises the systolic contraction amplitude. Heterogeneity of systolic Cai among cells due to diastolic S-CaOs also leads to heterogeneity of AP repolarization times, due, to heterogeneous Cai modulation of the Na/Ca exchanger, the non-specific cation channel and of the L type sarcolemmal Ca2+ channel. S-CaOs occurrence during a long AP plateau may also modulate the removal of voltage inactivation of L type Ca2+ channels and affect the likelihood of the occurrence of “early after depolarizations.” Thus, as a single entity, S-CaOs may be implicated in diverse manifestations of heart failure — impaired systolic performance, increased diastolic tonus and an increased probability for the occurrence of arrhythmias.

Key words

Cardiac cells sarcoplasmic reticulum spontaneous Ca2+oscillations orrhythmias 

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Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt 1992

Authors and Affiliations

  • E. G. Lakatta
    • 1
    • 2
  • A. Talo
    • 1
  • M. C. Capogrossi
    • 1
  • H. A. Spurgeon
    • 1
  • M. D. Stern
    • 1
  1. 1.Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on AgingNational Institutes of HealthBaltimoreUSA
  2. 2.Lab. Cardiovascular ScienceGerontol. Research Ctr. NIHBaltimoreUSA

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