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 I_Ca-L but decreased peak I_Ca-L. Decreased peak I_Ca-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 I_Ca-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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