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Simulating the Effects of Polyunsaturated Fatty Acids on Human Slowly Activating Delayed Rectifier Potassium Channel (KCNQ1 - KCNE1)

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Simulating the Effects of Polyunsaturated Fatty Acids on Human Slowly Activating Delayed Rectifier Potassium Channel (KCNQ1 - KCNE1)

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dc.contributor.advisor Ferrero De Loma-Osorio, José María es_ES
dc.contributor.advisor Severi, Stefano es_ES
dc.contributor.advisor Kharche, Sanjay es_ES
dc.contributor.author STARY, TOMAS es_ES
dc.date.accessioned 2012-05-07T12:37:29Z
dc.date.available 2012-05-07T12:37:29Z
dc.date.created 2011-09
dc.date.issued 2012-05-07
dc.identifier.uri http://hdl.handle.net/10251/15489
dc.description.abstract The consumption of omega-3 polyunsaturated fatty acids (PUFA) from fish oil is recommended to prevent arrhythmias and reduce risk of sudden cardiac death. PUFA modulate activity of various cardiac ion channels. The models of electrical activity of the heart based on mathematical formulation are a part of the efforts to improve the understanding and prediction of heart behaviour. The ion channels gating models are a basic part of models of cardiac electrical activity. The human slowly activated delayed rectifier potassium channel (IKs) is a key contributor to ventricle repolarization. The goal of this study is to determine the effects of PUFA on IKs. Further it aims to predict the effects of PUFA induced alteration in IKs on the ventricular action potential (AP). Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were used to perform the experiments. The Markov chain formulation of ion channel models constitutes an important improvement and is able to adequately describe the kinetic behaviour of the channel. The IKs Markovian model involves 17 conformation states and 15 parameters. This model was used to simulate the data obtained from voltage clamp experiment. The parameters of the model were identified using Nelder-Mead simplex method. The main results are the following. Acute exposure to PUFA increased IKs and augment the time constant. The Chronic exposure reduced IKs. Incorporating the identified model to human ventricle cell model caused AP prolongation in the Chronic case. The Acute EPA exposure caused AP shortening. The Acute DHA had no significant effect to AP in ten Tusscher et al. model and caused AP shortening in O'Hara et al. model. The Grandi et al. model was insensitive to IKs modifications. In conclusion the underlying mechanism of PUFA is very complex. Effects on the IKs and AP is may have proarrhythmic as well as antiarrhythmic consequences. Thus, the advice to increase the intake of PUFA should be adjusted with respect to pathophysiological setting of individual patient. es_ES
dc.format.extent 49 es_ES
dc.language Inglés es_ES
dc.publisher Universitat Politècnica de València es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject Polyunsaturated fatty acids es_ES
dc.subject Ion channel es_ES
dc.subject Arrhythmias es_ES
dc.subject Cardiac modeling es_ES
dc.subject.classification TECNOLOGIA ELECTRONICA es_ES
dc.subject.other Máster Universitario en Ingeniería Biomédica-Màster Universitari en Enginyeria Biomèdica es_ES
dc.title Simulating the Effects of Polyunsaturated Fatty Acids on Human Slowly Activating Delayed Rectifier Potassium Channel (KCNQ1 - KCNE1) es_ES
dc.type Tesis de máster es_ES
dc.rights.accessRights Cerrado es_ES
dc.contributor.affiliation Universitat Politècnica de València. Servicio de Alumnado - Servei d'Alumnat es_ES
dc.description.bibliographicCitation Stary, T. (2011). Simulating the Effects of Polyunsaturated Fatty Acids on Human Slowly Activating Delayed Rectifier Potassium Channel (KCNQ1 - KCNE1). http://hdl.handle.net/10251/15489 es_ES
dc.description.accrualMethod Archivo delegado es_ES


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