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Exploring the interplay between extracellular pH and Dronedarone's pharmacological effects on cardiac function.
de Lima Conceição, Michael Ramon; Teixeira-Fonseca, Jorge Lucas; Orts, Diego Jose Belato; Nascimento, Daniella Santos; Dantas, Cácia Oliveira; de Vasconcelos, Carla Maria Lins; Souza, Diego Santos; Roman-Campos, Danilo.
Afiliação
  • de Lima Conceição MR; Laboratório de CardioBiologia, Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
  • Teixeira-Fonseca JL; Laboratório de CardioBiologia, Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
  • Orts DJB; Laboratório de CardioBiologia, Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
  • Nascimento DS; Laboratory of Heart Biophysics, Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
  • Dantas CO; Laboratory of Heart Biophysics, Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
  • de Vasconcelos CML; Laboratory of Heart Biophysics, Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
  • Souza DS; Laboratory of Heart Biophysics, Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
  • Roman-Campos D; Laboratório de CardioBiologia, Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil. Electronic address: drcampos@unifesp.br.
Eur J Pharmacol ; 983: 176980, 2024 Nov 15.
Article em En | MEDLINE | ID: mdl-39241944
ABSTRACT
Dronedarone (DRN) is a clinically used drug to mitigate arrhythmias with multichannel block properties, including the sodium channel Nav1.5. Extracellular acidification is known to change the pharmacological properties of several antiarrhythmic drugs. Here, we explore how modification in extracellular pH (pHe) shapes the pharmacological profile of DRN upon Nav1.5 sodium current (INa) and in the ex vivo heart preparation. Embryonic human kidney cells (HEK293T/17) were used to transiently express the human isoform of Nav1.5 α-subunit. Patch-Clamp technique was employed to study INa. Neurotoxin-II (ATX-II) was used to induce the late sodium current (INaLate). Additionally, ex vivo Wistar male rat preparations in the Langendorff system were utilized to study electrocardiogram (ECG) waves. DRN preferentially binds to the closed state inactivation mode of Nav1.5 at pHe 7.0. The recovery from INa inactivation was delayed in the presence of DRN in both pHe 7.0 and 7.4, and the use-dependent properties were distinct at pHe 7.0 and 7.4. However, the potency of DRN upon the peak INa, the voltage dependence for activation, and the steady-state inactivation curves were not altered in both pHe tested. Also, the pHe did not change the ability of DRN to block INaLate. Lastly, DRN in a concentration and pH dependent manner modulated the QRS complex, QT and RR interval in clinically relevant concentration. Thus, the pharmacological properties of DRN upon Nav1.5 and ex vivo heart preparation partially depend on the pHe. The pHe changed the biological effect of DRN in the heart electrical function in relevant clinical concentration.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ratos Wistar / Canal de Sódio Disparado por Voltagem NAV1.5 / Dronedarona / Antiarrítmicos Limite: Animals / Humans / Male Idioma: En Revista: Eur J Pharmacol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ratos Wistar / Canal de Sódio Disparado por Voltagem NAV1.5 / Dronedarona / Antiarrítmicos Limite: Animals / Humans / Male Idioma: En Revista: Eur J Pharmacol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda