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Competing oscillators in cardiac pacemaking: historical background
Denis Noble1, Penelope J Noble, Martin Fink
1Department of Physiology, Anatomy and Genetics, Oxford University, Parks Rd, Oxford OX1 3PT, United Kingdom. denis.noble@dpag.ox.ac.uk
Circulation Research
|June 26, 2010
Summary
Cardiac cell oscillators, including membrane and calcium signals, entrain each other. The membrane oscillator can persist independently, unlike the calcium oscillator, which is crucial for cardiac pacemaker function.
Area of Science:
- Cardiology
- Biophysics
- Computational Biology
Background:
- Early models (1984-1985) explored interactions between membrane and calcium oscillators in the sarcoplasmic reticulum.
- Calcium-induced calcium release is an inherent process driving intracellular calcium oscillations.
Purpose of the Study:
- To synthesize historical findings on cardiac oscillator interactions.
- To elucidate the entrainment and asymmetry between membrane and calcium oscillators.
- To integrate insights from tissue-level studies and cardiac development on pacemaker function.
Main Methods:
- Review of historical models (1984-1985) of membrane and calcium oscillators.
- Analysis of calcium-induced calcium release mechanisms.
- Integration of findings from tissue-level and cardiac development studies.
Main Results:
- Membrane and intracellular calcium oscillators exhibit mutual entrainment.
- A key asymmetry exists: the membrane oscillator can sustain activity independently of the calcium oscillator.
- Calcium oscillator dependence on the membrane oscillator is primarily observed in pathological conditions.
Conclusions:
- Historical data support the proposed synthesis of cardiac oscillator interactions.
- The entrainment dynamics highlight the integrated action of the cardiac pacemaker.
- Understanding oscillator interdependence is vital for comprehending normal and pathological cardiac function.
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