A comparative review on heart ion channels, action potentials and electrocardiogram in rodents and human: extrapolation of experimental insights to clinic

Abstract

Electrocardiogram (ECG) is a non-invasive valuable diagnostic tool that is used in clinics for investigation and monitoring of heart electrical rhythm/conduction, ischemia/injury of heart, electrolyte disturbances and agents/drugs induced cardiac toxicity. Nowadays using animal models to study heart diseases such as electrical and mechanical disturbance is common. In addition, given to ethical consideration and availability, the use of small rodents has been a top priority for cardiovascular researchers. However, extrapolation of experimental findings from the lab to the clinic needs sufficient basic knowledge of similarities and differences between heart action potential and ECG of rodents and humans in normal and disease conditions. This review compares types of human action potentials, the dominant ion currents during action potential phases, alteration in ion channels activities in channelopathies-induced arrhythmias and the ECG appearance of mouse, rat, guinea pig, rabbit and human. Also, it briefly discusses the responsiveness and alterations in ECG following some interventions such as cardiac injury and arrhythmia induction. Overall, it provides a roadmap for researchers in selecting the best animal model/species whose studies results can be translated into clinical practice. In addition, this study will also be useful to biologists, physiologists, pharmacologists, veterinarians and physicians working in the fields of comparative physiology, pharmacology, toxicology and diseases.

Keywords: Action potential; ECG; Heart ion channels; Human; Rodents.

Fig. 1

A Schematic representation of the excitatory and conductive system of the heart and the time of impulse appearance (In hundredths of a second after starting at the SA node) in different parts of the heart. SA; sinoatrial, AV; atrioventricular, RA; right atrial, LA; left atrial, RV; right ventricle, LV; left ventricle. B cardiac fast and slow action potentials and different phases. C A normal electrocardiogram where P and T waves, QRS complex, intervals and segments are shown. ERP; effective refractory period, RRP; relative refractory period

Fig. 2

A Types of action potential of ventricular myocytes in human and rodents. B The main ion currents at different phase of the action potential in human. C The main ion currents at different phase of the action potential in rat and mouse. The direction of the arrows indicating the direction of ions flow

Fig. 3

Strips of lead II of electrocardiogram in human and redents and also location of electrodes connection to record human and rodent limbs leads of electrocardiogram. Consider the location of the positive and negative electrodes on the positions. Human, rabbit and guinea pig ECG have ST segment, however rat and mouse ECG have J wave. RA; right arm, LA; left arm, LL; left leg

Fig. 4

A ST segment elevation in human and rabbit ECG and J wave change in rat folowing to cardiac injury. B Ventricular torsade de points in human, rabbit and rat