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January 23, 1998Circulation Research534 citationsOpen Access

Mathematical Model of an Adult Human Atrial Cell

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ANAnders NygrenCFCéline FisetLFLudwik Firek

Key Result

A mathematical model of the human atrial myocyte showed that action potential shape is primarily determined by transient outward K+ current, I(sus), and L-type Ca2+ current.

Key Points

  • The aim is to develop a mathematical model of human atrial myocytes based on voltage-clamp data to understand ionic currents.
  • Developed a Hodgkin-Huxley-type model for the sarcolemma and a fluid compartment model for ionic concentrations.
  • Analyzed the effects of sustained outward K+ current (I[sus]), L-type Ca2+ current (I[Ca,L]), and transient outward K+ current on action potentials.
  • Used average data from voltage-clamp recordings from isolated human atrial myocytes.
  • The model reconstructs action potentials influenced by I(sus), I[Ca,L], and rapid delayed rectifier K+ current.
  • Modulation of I(sus) impacts the duration of the action potential depending on baseline current sizes.
  • Action potential shape is predominantly affected during peak and plateau phases by specific ionic currents.

Structured PICO

P
Population
Mathematical model of an adult human atrial myocyte based on averaged voltage-clamp data recorded from isolated single myocytes
I
Intervention
Mathematical modeling using a Hodgkin-Huxley-type equivalent circuit for the sarcolemma coupled with a fluid compartment model
O
Outcome
Reconstruction of action potential data and underlying ionic currentssurrogate

A mathematical model of the human atrial myocyte demonstrates that the sustained outward K+ current (I[sus]) plays a prominent role in determining action potential duration, which varies by physiological state.

Abstract

We have developed a mathematical model of the human atria myocyte based on averaged voltage-clamp data recorded from isolated single myocytes. Our model consists of a Hodgkin-Huxley-type equivalent circuit for the sarcolemma, coupled with a fluid compartment model, which accounts for changes in ionic concentrations in the cytoplasm as well as in the sarcoplasmic reticulum. This formulation can reconstruct action potential data that are representative of recordings from a majority of human atrial cells in our laboratory and therefore provides a biophysically based account of the underlying ionic currents. This work is based in part on a previous model of the rabbit atrial myocyte published by our group and was motivated by differences in some of the repolarizing currents between human and rabbit atrium. We have therefore given particular attention to the sustained outward K+ current (Isus), which putatively has a prominent role in determining the duration of the human atrial action potential. Our results demonstrate that the action potential shape during the peak and plateau phases is determined primarily by transient outward K+ current, I(sus) and L-type Ca2+ current (ICa,L) and that the role of I(sus) in the human atrial action potential can be modulated by the baseline sizes of I(Ca,L), I(sus) and the rapid delayed rectifier K+ current. As a result, our simulations suggest that the functional role of I(sus) can depend on the physiological/disease state of the cell.

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Cite This Study

Nygren et al. (1998) studied Human atrial myocyte electrophysiology. Mathematical model of human atrial myocyte was evaluated on Action potential reconstruction and ionic current determination. A mathematical model of the human atrial myocyte showed that action potential shape is primarily determined by transient outward K+ current, I(sus), and L-type Ca2+ current.

synapsesocial.com/papers/6a0cfba8b31ab1d6e01e7679https://doi.org/10.1161/01.res.82.1.63
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