Simulação de potencial de ação espontâneo em miócitos cardíacos do ventrículo esquerdo de camundongos

Abstract

Malignant ventricular arrhythmias are the major cause of death around the world. The beginning of an episode of arrhythmia is often associated with ectopic beats in the heart, also called extrasystole, or Spontaneous Action Potential (SAP). The development of SAP may be related to structural or molecular changes in ion channels and changes in intracellular calcium cycle. Abnormalities in calcium cycle can result in Spontaneous Calcium Transientes (SCT) and these can trigger SAP. Experimental studies show that the development of SCT is more common under β1-adrenergic stimulation. However, we found, in recent experiments, that the presence of episodes of SCT in healthy cardiomyocytes does not trigger the development of SAP. On the other hand, on mice presenting mutation of overexpression of NCX (NaCa) pump, SAP were observed in isolated cardiomyocytes and were related to episodes of SCT. Thus, we aimed, in this study, to simulate development of SAP using computational models developed for cardiomyocytes of left ventricle of mice. The computational models were able to reproduce the experimental scenarios described above, relating the development of SAP to the β-adrenergic stimulation and to the changes of ion channels as the NCX mutation. Therefore, the computational simulations showed in this work allow the best comprehension of the complex phenomena associated with cardiac arrhythmia.