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 (Ca(2+)) 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 Ca(2+)‐hemostasis.