Ethnic-Related Sodium Voltage-Gated Channel <i>α</i> Subunit 5 Polymorphisms Shape the In Vitro Pharmacological Action of Amiodarone upon Na<sub>v</sub>1.5
نویسندگان
چکیده
Nav1.5-derived Na+ current (INa) exerts a pivotal role in the depolarization phase of cardiomyocytes’ action potential, and, therefore, changes INa can contribute to fatal arrhythmias. Nav1.5 displays naturally occurring ethnicity-related polymorphisms, which might alter functioning and pharmacology channel. Some studies have shown how single-nucleotide polymorphism change response antiarrhythmic drugs. Investigations on arrhythmogenesis associated with its functional polymorphisms are currently growing as well possible variability pharmacotherapy among ethnic groups. The influence (S524Y, S1103Y, R1193Q, V1951L) responsiveness, selectivity, pharmacological efficacy clinically used amiodarone (AMIO) is not completely known. Our objectives were analyze biophysical aspects four before after exposure AMIO. Polymorphisms caused reduced AMIO potency compared wild type (WT), vary by up 4× between them. shifted voltage dependency for inactivation without significant effect voltage-dependent activation similar extent WT polymorphisms. recovery from was altered when WT. Finally, use differed studied groups, especially at more depolarized cell membrane. Thus, our work may guide future focusing efficiency treating different arrhythmias establish individualized guidelines depending validating findings using vivo studies. SIGNIFICANCE STATEMENT Sodium voltage-gated channel α subunit 5 (SCN5A) gene encodes Nav1.5, main cardiac Interestingly, found SCN5A. Amiodarone clinical practice, some effects attributed interaction Nav1.5. Important, variable patients. Here we show that SCN5A lead Nav1.5-amiodarone interaction, be cause observed usage amiodarone.
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ژورنال
عنوان ژورنال: Molecular Pharmacology
سال: 2021
ISSN: ['0026-895X', '1521-0111']
DOI: https://doi.org/10.1124/molpharm.120.000176