Abstract
Ventricular action potential is well-known because of its plateau phase with a spike-notch-dome morphology. As such, the morphology of action potential is necessary for ensuring a correct heart functioning. Any distraction from normal notch-dome morphology may trigger a circus movement reentry in the form of lethal ventricular fibrillation. When the epicardial action potential dome propagates from a site where it is maintained to regions where it has been lost, it gives rise to the proposed mechanism for the Brugada syndrome. Despite the impact of notch-dome dynamics on the heart function, no independent and explicit research has been performed on the simulation of notch-dome dynamics and morphology. In this paper, using a novel mathematical approach, a three-state variable model is proposed; we show that our proposed model not only can simulate morphology of action potential of ventricular cells but also can propose a biological reasonable tool for controlling of the morphology of action potential spike-notch-dome. We show that the processes of activation and inactivation of ionic gating variables (as positive or negative feedbacks on the voltage of cell membrane) and the ratio of their speeds (time constants) can be treated as a reasonable biological tool for simulating ventricular cell notch-dome. This finding may led to a new insight to the quantification of the health of a ventricular cell and may also propose a new drug therapy strategy for cardiac diseases.
Highlights
The so-called process, “excitation-contraction coupling” in the cardiac myocyte, is unique in that it is responsible for the coupling of electrical impulse to mechanical function
We showed that our simple three-state variable model can simulate action potential (AP) of ventricular cells
Our model was based on a novel idea that the ratio of the speeds of activation and inactivation gating variables in a ventricular cell model can govern the morphology of AP; we may regulate ND in AP via regulation of speed ratio
Summary
The so-called process, “excitation-contraction coupling” in the cardiac myocyte, is unique in that it is responsible for the coupling of electrical impulse to mechanical function. There are several ions, ion channels, and regulatory pathways participating in the generation of action potential (AP) of cardiac cells. Ionic channels are large transmembrane proteins having aqueous pores through which ions can flow down their electrochemical gradients. The dynamics of electrical conductance of an individual channel is controlled by its gate dynamics, i.e., gates’ speed. The speed of gates, i.e., their time constants, ionic concentrations, membrane voltage following time sequence, and various regulatory pathways determine the morphology of AP, which can be expressed as mathematical formalisms, making it feasible to use the computational approach to analyze and elucidate the underlying mechanisms of the whole cardiac cell
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