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.
Keywords: calcium; heart rate; potassium; sodium.
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