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Updated: Jul 16, 2026

Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection

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Cardiac Pacemaker Cells Harness Stochastic Resonance to Avoid Sinus Arrest.

Akihiro Okamura¹, Isabella K He¹, Alexander V Maltsev¹

¹National Institute on Aging, NIH, Baltimore, MD (A.O., I.K.H., Alexander V. Maltsev, R.B., S.T., M.W., M.D.S., E.G.L., V.A.M.).

Circulation Research

|July 15, 2026

Summary

Pacemaker cells in the heart utilize stochastic resonance, a phenomenon amplified by coupled signaling, to ensure regular heartbeat initiation, especially during slow heart rates. This mechanism helps prevent cardiac arrest by harnessing biological noise.

Keywords:

animals biology heart rate membrane potentials rabbits

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Area of Science:

Cardiac Electrophysiology
Computational Biology
Cellular Signaling

Background:

The sinoatrial node (SAN) is the heart's primary pacemaker.
Recent imaging reveals heterogeneous signals, including subthreshold potentials in dormant cells, exiting the SAN.
The role of these signals in heartbeat generation remains unclear.

Purpose of the Study:

To test the hypothesis that pacemaker cells use stochastic resonance for fail-safe operation, particularly at low heart rates near sinus arrest.
To investigate the contribution of heterogeneous signals to heartbeat generation.

Main Methods:

Perforated-patch recordings of membrane potential and Ca signals in rabbit SAN cells exposed to controlled currents.
Imaging of Ca signals in intact mouse SAN tissue.
Multiscale computational modeling at subcellular, cellular, and tissue levels.

Main Results:

Noise currents restored firing in dormant SAN cells and improved rhythmicity in irregularly firing cells, demonstrating stochastic resonance.
SAN cells exhibited a resonance spectrum, indicating frequency-specific responses to noise.
Coupled electrical and Ca signaling amplified stochastic resonance, enhancing action potential generation.
Models showed that adding noise currents enabled firing under conditions where it would otherwise cease.

Conclusions:

Sinoatrial node cells employ stochastic resonance, amplified by coupled signaling, for rhythmic heartbeat initiation, especially at low rates.
This mechanism may prevent sinus arrest during conditions of increased biological noise, such as aging or parasympathetic stimulation.