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

Ageing is associated with an increased risk of cardiovascular disease and arrhythmias, with the most common arrhythmia being found in the atria of the heart. Little is known about how the normal atria of the heart remodel with age and thus why dysfunction might occur. We report alterations to the atrial systolic Ca²⁺ transient that have implications for the function of the atrial in the elderly. We describe a novel mechanism by which increased Ca buffering can account for changes to systolic Ca²⁺ in the old atria. The present study helps us to understand how the processes regulating atrial contraction are remodelled during ageing and provides a basis for future work aiming to understand why dysfunction develops.

Many cardiovascular diseases, including those affecting the atria, are associated with advancing age. Arrhythmias, including those in the atria, can arise as a result of 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 atria. Using single atrial myocytes from young and old Welsh Mountain sheep, we show the free Ca²⁺ transient amplitude and rate of decay of systolic Ca²⁺ decrease with age, whereas 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 sarcoendoplasmic reticulum calcium transport ATPase 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 during ageing. The results of the present study highlight a novel mechanism by which increased Ca buffering decreases systolic Ca²⁺ in old atria. Furthermore, for the first time, we have shown that SR Ca content is increased in old atrial myocytes.