Human myocardial Na,K-ATPase — quantification, regulation and relation to Ca

Time for primary review 26 days. The Na,K-ATPase (sodium, potassium adenosine triphosphatase) or the Na,K-pump is an ubiquitous enzyme which performs the active transport of Na and K across the cell membrane 1. Thus, by hydrolysing ATP the Na,K-ATPase pumps 3 Na ions out of the cell and 2 K ions into the cell. Hence, Na,K-ATPase is of importance for the characteristic distribution of these cations across the cell membrane and for generation of the membrane potential; thus optimum Na,K-ATPase function is required to ensure excitability and conduction. By generating the Na gradient across the sarcolemma, Na,K-ATPase creates a driving force for active Ca extrusion via the Na — Ca exchanger embedded in the membrane. Together with the Ca-ATPase located in the sarcolemma and in the membrane of the sarcoplasmic reticulum, the Na-Ca exchanger is of importance for maintaining low diastolic Ca concentration 2. When muscular cells are depolarized intracellular Ca rises as much as 10 fold to around 1 μmol×litre−1 3. Subsequently Ca binds to troponin C triggering the force generating interaction between actin and myosin. Thus, Na,K-ATPase has the capacity for influencing muscular force generation. It might be noted that whereas the Na,K-pump utilizes around 4% of myocardial energy expenditure to maintain Na,K gradients, as much as 30% is used to fuel the Ca-ATPase 4. Cardiac glycosides bind to the Na,K-ATPase in a 1: 1 ratio 5, and myocardial Na,K-ATPase is generally accepted to be the target for its positive inotropic action eliciting an increase in the availability of Ca to the contractile proteins in heart cells 6. Cardiac glycosides bind with high affinity and specificity to an inhibitory site on the α subunit of Na,K-ATPase facing the outside of the cell, resulting in the complete inhibition of Na and K … * Corresponding author. Tel. (+45) 3545 2871; Fax: (+45) 3138 3186.