Comput. Biol. Med. - Modeling gender effects on electrical activity of single ventricular myocytes.

Tópicos

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Resumo

In this study we investigate the mechanisms underlying gender differences in the generation of arrhythmias in the long QT and Brugada syndromes. Simulations were conducted at the single myocyte level using a detailed mathematical model of human ventricular myocytes. Given the scarce human data on the gender-related differences in single cardiac cells, we assumed gender-related differences in five ionic-current systems: fast sodium current (INa), slowly inactivating late sodium current (INal), transient outward potassium current (Ito), slow delayed rectifier potassium current (IKs), and calcium current through the L-type channel (ICa(L)), based on experimental results obtained in canine myocytes. Our modeling results suggest that in left ventricular myocytes, enhanced INal under conditions of reduced repolarization reserve results in sex-dependent development of early afterdepolarizations (EADs) in the post-pause action potentials (APs). Moreover, this modeling study demonstrates increased propensity for the development of the loss of the AP dome in male epicardial myocytes of the right ventricle compared with other types of myocytes from the left and right ventricles. Finally, we also found a slight effect of INal on gender-dependent loss of AP dome in epicardial right ventricular myocytes. In conclusion, at the cellular level, gender differences in the development of EADs and the propensity to develop the loss of the AP dome can be attributed to male/female related differences in INa, INal, Ito, IKs, and ICa(L).

Resumo Limpo

studi investig mechan under gender differ generat arrhythmia long qt brugada syndrom simul conduct singl myocyt level use detail mathemat model human ventricular myocyt given scarc human data genderrel differ singl cardiac cell assum genderrel differ five ioniccurr system fast sodium current ina slowli inactiv late sodium current inal transient outward potassium current ito slow delay rectifi potassium current ik calcium current ltype channel ical base experiment result obtain canin myocyt model result suggest left ventricular myocyt enhanc inal condit reduc repolar reserv result sexdepend develop earli afterdepolar ead postpaus action potenti ap moreov model studi demonstr increas propens develop loss ap dome male epicardi myocyt right ventricl compar type myocyt left right ventricl final also found slight effect inal genderdepend loss ap dome epicardi right ventricular myocyt conclus cellular level gender differ develop ead propens develop loss ap dome can attribut malefemal relat differ ina inal ito ik ical

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