What makes the sinoatrial node tick? A question not for the faint of heart

Philos Trans R Soc Lond B Biol Sci. 2023 Jun 19;378(1879):20220180. doi: 10.1098/rstb.2022.0180. Epub 2023 May 1.

Abstract

Even before the sinoatrial node (SAN) was discovered, cardiovascular science was engaged in an active investigation of when and why the heart would beat. After the electrochemical theory of bioelectric membrane potentials was formulated and the first action potentials were measured in contracting muscle cells, the field became divided: some investigators studied electrophysiology and ion channels, others studied muscle contraction. It later became known that changes in intracellular Ca2+ cause contraction. The pacemaking field was reunited by the coupled-clock theory of pacemaker cell function, which integrated intracellular Ca2+ cycling and transmembrane voltage into one rhythmogenic system. In this review, we will discuss recent discoveries that contextualize the coupled-clock system, first described in isolated SAN cells, into the complex world of SAN tissue: heterogeneous local Ca2+ releases, generated within SAN pacemaker cells and regulated by the other cell types within the SAN cytoarchitecture, variably co-localize and synchronize to give rise to relatively rhythmic impulses that emanate from the SAN to excite the heart. We will ultimately conceptualize the SAN as a brain-like structure, composed of intercommunicating meshworks of multiple types of pacemaker cells and interstitial cells, intertwined networks of nerves and glial cells and more. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

Keywords: calcium; local calcium releases; pacemaker cell; rhythm; sinoatrial node; telocyte.

Publication types

  • Review
  • Research Support, N.I.H., Intramural

MeSH terms

  • Action Potentials / physiology
  • Calcium / metabolism
  • Myocytes, Cardiac* / metabolism
  • Sinoatrial Node* / metabolism

Substances

  • Calcium