Role of myofilaments and calcium handling in left ventricular relaxation

W. C. Hunter

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Myocardial relaxation is governed by the interplay of two macromolecular systems: (1) myofilaments and (2) calcium extruding pumps/exchangers. In myocardium from failing hearts, both systems act more slowly than normal, and cause relaxation to decelerate, which may impede early rapid filling and can often limit cardiac pumping abilitye - especially during exercise. Gene-based therapy to augment sluggish SERCA pumps is a possibility being currently investigated in research laboratories. In normal myocardium, the rate of dissociation of myosin crossbridges sets the rate of relaxation. In this case, relaxation is characterized by two features: (1) load-dependence and (2) displacement-dependence. Load-dependence derives from cooperative mechanisms acting among ensembles of cross-bridges and myofilament regulatory proteins (troponin, tropomyosin); it allows contraction to be prolonged when more crossbridges are attached and mutually support each other. The rate of relaxation can still be rapid, however, as this cooperative system begins to collapse. Displacement-dependence is more important later in contraction, because tenuous crossbridge attachments cannot easily re-form after being disrupted when myofilaments slide along each other. Myofilaments control normal relaxation because the calcium extruding systems reduce calcium to near diastolic levels relatively early; however, when the relative timing of crossbridge dissociation versus calcium sequestration is altered, and calcium uptake is slowed (relative to crossbridges), then removal of calcium can become rate limiting instead. In this case, load- and displacement-dependence are less marked. Both the timing of calcium removal and the sensitivity of the myofilaments to calcium affect relaxation timing.

Original languageEnglish (US)
Pages (from-to)443-457
Number of pages15
JournalCardiology Clinics
Volume18
Issue number3
DOIs
StatePublished - 2000

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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