| Texto completo | |
| Autor(es): |
de Conceicao, Michael Ramon Lima
;
Teixeira-Fonseca, Jorge Lucas
;
Marques, Leisiane Pereira
;
Souza, Diego Santos
;
Roman-Campos, Danilo
Número total de Autores: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | European Journal of Pharmacology; v. 960, p. 12-pg., 2023-10-24. |
| Resumo | |
Introduction: Amiodarone (AMD) is a clinically used drug to treat arrhythmias with significant effect upon the cardiac sodium channel Na(v)1.5. AMD has a pKa of 6.56, and changes in extracellular pH (pHe) may alter its pharmacological properties. Here we explored how changes in pHe impacts the pharmacological properties of AMD upon human-Na(v)1.5-sodium-current (I-Na) and in ex vivo rat hearts.Methods: Embryonic-human-kidney-cells (HEK293) were used to transiently express the human alpha-subunit of Na(V)1.5 channels and the isolated heart of Wistar rats were used. Patch-Clamp technique was deployed to study I-Na and for electrocardiogram (ECG) evaluation the ex vivo heart preparation in the Langendorff system was applied.Results: The potency of AMD upon peak I-Na was similar to 25x higher in pHe 7.0 when compared to pHe 7.4. Voltage dependence for activation did not differ among all groups. AMD shifted the steady-state inactivation curve to more hyperpolarized potentials, with similar magnitudes for both pHes. The recovery from I-Na inactivation was delayed in the presence of AMD with similar profile in both pHes. Interestingly, the use-dependent properties of AMD was distinct at pHe 7.0 and 7.4. Finally, AMD was able to change the ex vivo ECG profile, however at pHe 7.0+AMD a larger increase in the RR and QRS duration and in the QT interval when compared to pHe 7.4 was found.Conclusions: The pharmacological properties of AMD upon Na(V)1.5 and isolated heart preparation depends on the pHe and its use in vivo during extracellular acidosis may cause a distinct biological response in the heart tissue. (AU) | |
| Processo FAPESP: | 21/05584-7 - Avaliação da toxicidade aguda e crônica ao coração e ao cérebro expostos a pesticidas encontrados na água potável do Brasil |
| Beneficiário: | Danilo Roman Campos |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2 |
| Processo FAPESP: | 19/18918-0 - Participação do óxido nítrico nas arritmias cardíacas durante o Hipotireoidismo |
| Beneficiário: | Diego Santos de Souza |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 21/15122-0 - Cardiotoxicidade induzida pelo pesticida tebuconazol em camundongos: da concepção a vida adulta |
| Beneficiário: | Leisiane Pereira Marques |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 20/14635-1 - Modelagem de doenças monogênicas para estudos fisiopatológicos e testes farmacológicos utilizando células especializadas derivadas de iPSCs |
| Beneficiário: | João Bosco Pesquero |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |