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.