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Na + -Handling Na + -handling is the primary determinant of cardiomyocyte excitability ( + channels, which determines the action potential V max and APA and initiates downstream Ca 2+ -handling for contraction ( + /Ca 2+ exchanger (NCX1) contributes to cytosolic Ca 2+ clearance in diastole, while the ubiquitous Na + /K + -ATPase (NKA) energetically maintains the stable cardiac RMP ( + -handling, centring around an increase in intracellular Na + concentration (Wu and Corr, 1995)