Dynamic regulation of pacemaker activity by the Na+-K+ pump

Stefano Morotti, Joshua R.St Clair, Catherine Proenza, Eleonora Grandi

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations


The role of Na+ homeostasis in cardiac pacemaking is not well established. Blocking of the Na+-K+ ATPase (NKA) to raise intracellular Na+ concentration ([Na+]i) in ventricles, thereby reducing Ca2+ removal by the Na+-Ca2+ exchanger (NCX), is widely used to improve cardiac inotropy in patients with congestive heart failure. However, NKA-blocking agents have a narrow therapeutic window, and cardiotoxic effects are common, as excessive Ca2+ accumulation is pro-arrhythmic and decreases lusitropy. Here, we updated an existing mathematical model of the mouse sinoatrial node (SAN) myocyte to determine the effects of increasing [Na+]i on pacemaker cell function, and test whether high [Na+]i levels have disrupting effects similar to those of cardiac glycosides in the ventricle. Model parameter sensitivity analysis revealed that NKA modulation impacts Na+ and Ca2+ homeostasis, as well as several action potential (AP) characteristics. NKA dynamically modulates cell automaticity: upon NKA inhibition SAN firing rate instantaneously increases, due to direct effects on membrane potential (Em) dynamics, and slowly continues to increase over time, while Na+ and Ca2+ accumulate. Simulations of various degrees of block showed that Na+ overload can even stop SAN firing. Thus [Na+]i plays a fundamental role in the regulation of pacemaker activity.

Original languageEnglish (US)
Title of host publicationComputing in Cardiology Conference, CinC 2016
PublisherIEEE Computer Society
Number of pages4
ISBN (Electronic)9781509008964
StatePublished - Mar 1 2016
Event43rd Computing in Cardiology Conference, CinC 2016 - Vancouver, Canada
Duration: Sep 11 2016Sep 14 2016


Other43rd Computing in Cardiology Conference, CinC 2016

ASJC Scopus subject areas

  • Computer Science(all)
  • Cardiology and Cardiovascular Medicine


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