| Grant number: | 18/20777-3 |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| Start date: | May 01, 2019 |
| End date: | June 30, 2022 |
| Field of knowledge: | Biological Sciences - Pharmacology - Cardiorenal Pharmacology |
| Principal Investigator: | Danilo Roman Campos |
| Grantee: | Julliane Vasconcelos Joviano dos Santos |
| Host Institution: | Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil |
Abstract Abstract: The cardiac cycle depends on the proper function of the excitation contraction coupling in ventricular myocytes (VMs), which has ion channels as primary player present on cell membrane of VMs. Nav 1.5, encoded by SCN5A gene, is the primary cardiac sodium channel. Sodium current (INa) has two components: the transient peak (INa-P) and the late (INa-L). In the cardiac cycle, acquired and inherited channelopathies usually causes altered action potential (AP) in VMs. Polymorphism are defined by replacement of one nucleotide in the DNA sequence observed in e 1% of population. In Brazil, due to migration, it is observed strong influence of African, European and Asian ethnics, which are found to have S524Y, S1103Y, R1193Q e V1951L polymorphisms in Nav 1.5. Polymorphisms may lead to altered biophysical and pharmacological properties of Nav 1.5 and, once associated to other mutations, may cause disease linked mutation (e.g Long QT Syndrome). Despite of great important of Nav 1.5 in the cardiac cycle, it is not fully understood how polymorphism impacts on biophysical and pharmacological properties of Nav 1.5. Thus, we intent to: 1) understand how ethnic linked polymorphism impact on biophysical and 2) pharmacological properties (potency, efficacy and selectivity) of antiarrhythmic drugs (amiodarone and ranolazine) on Nav 1.5. In order to achieve the main goal we will take advantage of: point mutation, heterologous expression and patch-clamp technique. In the future we intent to study arrhythmic disease related mutation found in Brazilian population and how it influences antiarrhythmic therapy. The proposed project is associated to Young Investigation Project of the Principal Investigation. | |
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