Calcium cycling in the aged heart

Y. Y. Zhou, E. G. Lakatta, R. P. Xiao

Research output: Contribution to journalArticlepeer-review

Abstract

One of the most important hallmarks of the aged heart is altered calcium homeostasis, possibly due to age-associated alterations in several major calcium cycling processes involved in cardiac excitation-contraction coupling. During ageing, the magnitude of the L-type Ca2+ channel current (I(Ca),L) becomes significantly increased in parallel with the enlargement of cardiac myocytes, resulting in an unaltered I(Ca),L density. Since the inactivation of I(Ca),L is slowed, and the action potential duration is prolonged, the net Ca2+ influx during each action potential is increased in cells of senescent myocardium relative to cells of adult control. While neither mRNA nor protein levels of the sarcoplasmic reticulum (SR) Ca2+ release channel (ryanodine receptor) significantly change with advancing adult age, the mRNA abundance and the density of SR Ca2+ pump decrease with ageing and are associated with a diminished SR Ca2+ sequestration rate in the aged heart. In addition, cardiac chronotropic and inotropic responses to β-adrenergic receptor stimulation are also reduced with advancing age. The multiple changes in Ca cycling that occur during ageing result in an augmented Ca2+ influx, slowed SR Ca2+ sequestration and prolonged durations of the Ca(i) transient and contraction. These alterations which prolong electromechanical systole may be construed as an adaptation in that they prolong the force-bearing capacity of the senescent cells following excitation. This is helpful with respect to maintaining the cardiac function in the aged heart. However, they also increase the risk of Ca2+ overload and Ca2+-dependent arrhythmias during stress in the senescent heart. Although reduced β-adrenergic responses with ageing contribute to diminished contraction reserve, these may be viewed in part, as adaptive, in that they protect against Ca2+ overload during stress.

Original languageEnglish (US)
Pages (from-to)88-96
Number of pages9
JournalAsia Pacific Heart Journal
Volume8
Issue number2
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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