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

Research output: Contribution to journalArticle

Abstract

The cytosolic Ca2+ (Ca(i)) 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 Ca(i) oscillations (S-CaOs), i.e., not triggered by sarcolemmal depolarization. The local increase in Ca(i) due to S-CaOs is equivalent to that induced by an AP. Heterogeneity of diastolic Ca(i) 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 Ca(i) 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 Ca(i) 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 after contraction 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 Ca(i) levels and sarcomere length inhomogeneities in response a subsequent AP; this heterogeneity compromises the systolic contraction amplitude. Heterogeneity of systolic Ca(i) among cells due to diastolic S-CaOs also leads to heterogeneity of AP repolarization times, due, to heterogeneous Ca(i) 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.

Original languageEnglish
Pages (from-to)93-104
Number of pages12
JournalBasic Research in Cardiology
Volume87
Issue numberSUPPL. 2
Publication statusPublished - 1992

Fingerprint

Sarcoplasmic Reticulum
Action Potentials
Sarcomeres
Cations
Systolic Heart Failure
Myofibrils
Cardiac Arrhythmias
Membranes

Keywords

  • Cardiac cells
  • Orrhythmias
  • Sarcoplasmic reticulum
  • Spontaneous Ca oscillations

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lakatta, E. G., Talo, A., Capogrossi, M. C., Spurgeon, H. A., & Stern, M. D. (1992). Spontaneous sarcoplasmic reticulum Ca2+ release leads to heterogeneity of contractile and electrical properties of the heart. Basic Research in Cardiology, 87(SUPPL. 2), 93-104.

Spontaneous sarcoplasmic reticulum Ca2+ release leads to heterogeneity of contractile and electrical properties of the heart. / Lakatta, E. G.; Talo, A.; Capogrossi, M. C.; Spurgeon, H. A.; Stern, M. D.

In: Basic Research in Cardiology, Vol. 87, No. SUPPL. 2, 1992, p. 93-104.

Research output: Contribution to journalArticle

Lakatta, EG, Talo, A, Capogrossi, MC, Spurgeon, HA & Stern, MD 1992, 'Spontaneous sarcoplasmic reticulum Ca2+ release leads to heterogeneity of contractile and electrical properties of the heart', Basic Research in Cardiology, vol. 87, no. SUPPL. 2, pp. 93-104.
Lakatta, E. G. ; Talo, A. ; Capogrossi, M. C. ; Spurgeon, H. A. ; Stern, M. D. / Spontaneous sarcoplasmic reticulum Ca2+ release leads to heterogeneity of contractile and electrical properties of the heart. In: Basic Research in Cardiology. 1992 ; Vol. 87, No. SUPPL. 2. pp. 93-104.
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AU - Stern, M. D.

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