Influence of SR Ca(2+)-ATPase and Na(+)-Ca(2+)-exchanger on the force-frequency relation.

The data presented indicate that altered systolic and diastolic function in failing human hearts may result from altered expression of calcium cycling proteins. Decreased systolic force production and inversion of the force-frequency relation seem to be related to reduced protein levels of SR Ca2+ ATPase and/or to increased protein levels of the Na(+)-Ca2+ exchanger resulting in an increased ratio of Na(+)-Ca2+ exchanger to SR Ca2+ ATPase. Impaired diastolic function may result from reduced SR Ca2+ ATPase and is most pronounced in failing hearts with lack of upregulation of the Na(+)-Ca2+ exchanger. Thus, failing hearts with reduced SR Ca2+ ATPase protein levels and unchanged Na(+)-Ca2+ exchanger protein levels exhibit severe impairment of both systolic and diastolic function.