Heart rate changes and myocardial sodium

Gabrielle Nelson, Bo Ye, Morgan Schock, Daniel L. Lustgarten, Elisabeth K. Mayhew, Bradley M. Palmer, Markus Meyer

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2 Scopus citations


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.

Original languageEnglish (US)
Article numbere15446
JournalPhysiological Reports
Issue number17
StatePublished - Sep 2022

Bibliographical note

Funding Information:
M. Meyer was supported by the Engdahl Family Foundation and a National Institutes of Health Grant (R01 HL‐122744).

Publisher Copyright:
© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.


  • calcium
  • heart rate
  • potassium
  • sodium


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