Mathematical model of action potential and Ca2+ transport in ventricular myocytes of neonatal rats

Author(s)

Natália Ferreira Oshiyama

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Engenharia Elétrica e de Computação
• Defense date: 2014-03-28

Examining board members

José Wilson Magalhães Bassani; Emiliano Horacio Medei; Wamberto Antonio Varanda; Wilson Nadruz Junior; Eduardo Tavares Costa

• Advisor: José Wilson Magalhães Bassani; Rosana Almada Bassani

Abstract

The action potential (AP), a change in electrical potential across the membrane (Em), is generated by ionic fluxes through channels and transporters, of which function and expression may be affected by hormones, neurotransmitters, drugs and toxins. Computational models constitute an important tool for the study of this highly non-linear and complex system. In this work, a model of AP and Ca2+ transport in ventricular cells of neonatal rats was developed. It was necessary to measure the intracellular Na+ concentration ([Na+]i) and the Na+ current (INa), for which information in the literature is scarce, and the Ca2+ current (ICa), as well as the outward transient (Ito) and delayed rectifier (IK) K+ currents, in addition to the AP itself, to improve the accuracy of the model. Measurements from adult rat myocytes were also made in order to compare these developmental phases. It was observed that neonatal rat cells are less excitable, which could be explained by a ~10 mV shift to the right of the channel activation curve, i.e., Na+ channels activation occured at less negative Em value and over a higher range of Em compared to adult cells. On the other hand, INa density was twice as great as that in adults. This might promote increase in [Na+]i during activity in cells from newborns, which was confirmed by measurement of [Na+]i. Nonetheless, significant Na+ accumulation was suppressed when ICa and the Na+ / Ca2+ exchanger (NCX) were inhibited, which indicates that the increase in [Na+]i probably depends more on Ca2+ efflux via NCX than on the influx through sarcolemmal Na+ channels. The longer AP duration in neonatal myocytes could be explained by the lower density of the repolarizing currents (Ito and IK). However, age-dependent difference in ICa density was not observed. Simulation data agreed with experimental data from this laboratory regarding the sarcoplasmic reticulum (SR) as the main source of Ca2+ during excitation-contraction coupling and the lower SR fractional release in neonatal than in adult myocytes. In conclusion, the present model may be used to predict possible electrophysiological alterations in developing cardiomyocytes under different conditions. (AU)

• FAPESP's process: 11/19805-3 - Mathematical model of action potential and Ca2+ transport in neonatal rat ventricular myocyte.
• Grantee: Natalia Ferreira Oshiyama
• Support Opportunities: Scholarships in Brazil - Doctorate