Research ArticlePhysiology

A coupled-clock system drives the automaticity of human sinoatrial nodal pacemaker cells

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Sci. Signal.  12 Jun 2018:
Vol. 11, Issue 534, eaap7608
DOI: 10.1126/scisignal.aap7608

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Two clocks for a steadily beating heart

The sinoatrial node is the endogenous pacemaker of the heart. Using isolated human sinoatrial node cells, Tsutsui et al. investigated the molecular mechanisms that enabled these cells to generate electrical signals at regular intervals to trigger rhythmic cardiac contractions. They found that periodic oscillations in Ca2+ and membrane potentials formed the basis for two interdependent “clocks” that together regularly generated spontaneous electrical signals. These clocks were uncoupled in human sinoatrial node cells that were not beating. Moreover, signaling downstream of β-adrenergic receptors enhanced the coupling between these two clocks and could induce electrical activity in some cells that were not beating. Understanding the mechanisms that generate pacemaking activity in human sinoatrial node cells may lead to the development of better therapies for sinus arrest, a condition that is caused by malfunction of the sinoatrial node and currently treated with a permanently implanted pacemaker.