Heart rate changes and myocardial sodium

Historic studies with sodium ion (Na⁺) micropipettes and first-generation fluorescent probes suggested that an increase in heart rate results in higher intracellular Na⁺-levels. Using a dual fluorescence indicator approach, we simultaneously assessed the dynamic changes in intracellular Na⁺ and calcium (Ca²⁺) with measures of force development in isolated excitable myocardial strip preparations from rat and human left ventricular myocardium at different stimulation rates and modeled the Na⁺-effects on the sodium-calcium exchanger (NCX). To gain further insight into the effects of heart rate on intracellular Na⁺-regulation and sodium/potassium ATPase (NKA) function, Na⁺, and potassium ion (K⁺) levels were assessed in the coronary effluent (CE) of paced human subjects. Increasing the stimulation rate from 60/min to 180/min led to a transient Na⁺-peak followed by a lower Na⁺-level, whereas the return to 60/min had the opposite effect leading to a transient Na⁺-trough followed by a higher Na⁺-level. The presence of the Na⁺-peak and trough suggests a delayed regulation of NKA activity in response to changes in heart rate. This was clinically confirmed in the pacing study where CE-K⁺ levels were raised above steady-state levels with rapid pacing and reduced after pacing cessation. Despite an initial Na⁺ peak that is due to a delayed increase in NKA activity, an increase in heart rate was associated with lower, and not higher, Na⁺-levels in the myocardium. The dynamic changes in Na⁺ unveil the adaptive role of NKA to maintain Na⁺ and K⁺-gradients that preserve membrane potential and cellular Ca²⁺-hemostasis.