Παρασκευή 28 Ιουλίου 2017

Increased Ca buffering underpins remodelling of Ca2+ handling in old sheep atrial myocytes

Abstract

Many cardiovascular diseases, including those affecting the atria, are associated with advancing age. Arrhythmias, including those in the atria, can arise due to electrical remodelling or alterations in Ca2+ homeostasis. In the atria, age-associated changes in the action potential have been documented. However, little is known about remodelling of intracellular Ca2+ homeostasis in the healthy aged heart.

Using single atrial myocytes from young and aged Welsh Mountain sheep, we show the free Ca2+ transient amplitude and rate of decay of systolic Ca2+ decrease with age while sarcoplasmic reticulum (SR) Ca content increases. An increase in intracellular Ca buffering explains both the decrease in Ca2+ transient amplitude and decay kinetics in the absence of any change in SERCA function. Ageing maintained the integrated Ca2+ influx via ICa-L but decreased peak ICa-L. Decreased peak ICa-L was found to be responsible for the age-associated increase in SR Ca content but not the decrease in Ca2+ transient amplitude. Instead decreased peak ICa-L offsets increased SR load such that Ca2+ release from the SR was maintained in ageing.

Our results highlight a novel mechanism by which increased Ca buffering decreases systolic Ca2+ in old atria. Furthermore, we have shown for the first time that SR Ca content is increased in old atrial myocytes.

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