INFLUENCE OF SR CA2-ATPASE AND NA+-CA2+-EXCHANGER ON THE FORCE-FREQUENCY RELATION()

The data presented indicate that altered systolic and diastolic functi on in failing human hearts may result from altered expression of calci um 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 reduced SR Ca2ATPase protein levels levels of the Na+-Ca2+ exchanger resulting in an increased ratio of Na+-Ca2+ exchanger to SR Ca2+ ATPase. Impaired dia stolic function may result from reduced SR Ca2+ ATPase and is most pro nounced in failing hearts with lack of upregulation of the Na+-Ca2+ ex changer. Thus, failing hearts with reduced SR Ca2+ ATPase protein leve ls and unchanged Na+-Ca2+ exchanger protein levels exhibit severe impa irment of both systolic and diastolic function.