During the last decade there was accumulating evidence Ž. that alterations of excitation-contraction EC coupling may play a critical role in the pathophysiology of myocardial failure. EC-coupling comprises processes involved in calcium activation of contractile proteins and the subsequent Ž removal of calcium facilitating relaxation for review see w x. 1. The initial event is depolarisation of the membrane which opens voltage-gated, dihydropyridine-sensitive sar-Ž. colemmal calcium channels dihydropyridine receptors allowing an influx of calcium into the myocyte. There is a close proximity between one or a few sarcolemmal calcium channels and one or a few calcium channels of the Ž. sarcoplasmic reticulum ryanodine receptors. This may enable calcium influx through one opening of a single sarcolemmal calcium channel to increase a local pool of calcium sufficiently to open adjacent ryanodine receptors to release calcium. This local, punctate, increase of calcium is termed calcium spark according to its visualization wx by confocal microscopy 2. It is the sum of these local calcium releases which generate a global cytoplasmic increase in calcium which causes activation of contractile proteins. The global increase in calcium is immediately followed by calcium removal resulting in subsequent deactivation of the contractile machinery. Calcium removal from the cytosol occurs by activity of the sarcoplasmic reticulum calcium pump and by exchange of calcium for q 2q wx sodium by the sarcolemmal Na-Ca-exchanger 1. Defective EC-coupling in heart failure may result from altered density or function of proteins relevant for calcium homeostasis. Knowledge of these alterations is a pre-