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Feedback-control induced pattern formation in cardiac myocytes: a mathematical modeling study.

Stephen A Gaeta¹, Trine Krogh-Madsen, David J Christini

¹Greenberg Division of Cardiology, Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10065, USA.

Journal of Theoretical Biology

|July 13, 2010

Summary

Cardiac alternans, a heart rhythm disturbance, can manifest as subcellular alternans. This study reveals how specific pacing strategies induce subcellular alternans by altering calcium-voltage coupling, demonstrating a biological Turing instability.

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Area of Science:

Cardiology
Biophysics
Computational Biology

Background:

Cardiac alternans involves beat-to-beat alternations in myocyte action potential duration and calcium transients.
Subcellular alternans, where adjacent myocyte regions alternate out-of-phase calcium transients, has been recently observed.
Previous theories linked subcellular alternans to Turing instability in specific cardiac myocyte types, but lacked experimental verification.

Purpose of the Study:

To investigate the mechanism of dynamically induced subcellular alternans.
To determine if alternans control pacing can induce subcellular alternans in cardiac myocytes with positive calcium-to-voltage coupling.
To elucidate the role of Turing-type instabilities in subcellular alternans formation.

Main Methods:

Theoretical modeling of cardiac myocyte electrophysiology and calcium dynamics.
Application of a feedback control algorithm ('alternans control') during pacing simulations.
Analysis of calcium-voltage (Ca<-->V(m)) and voltage-calcium (V(m)<-->Ca) coupling dynamics.

Main Results:

Alternans control pacing modifies the effective voltage-calcium coupling (V(m)<-->Ca).
This modification predicts subcellular alternans via Turing instability in myocytes with positive Ca<-->V(m) coupling.
The findings align with and extend previous theoretical and experimental observations on subcellular alternans.

Conclusions:

Subcellular alternans can be dynamically induced by specific pacing protocols.
Alternans control pacing facilitates subcellular alternans by altering V(m)<-->Ca coupling, enabling Turing instability.
This study provides a clear example of a biological Turing instability with identifiable diffusing morphogens in cardiac cells.