title: Carvacrol modulates voltage-gated sodium channels kinetics in dorsal root ganglia.
abstract: Recent studies have shown that many of plant-derived compounds interact with specific ion channels and thereby modulate many sensing mechanisms, such as nociception. The monoterpenoid carvacrol (5-isopropyl-2-methylphenol) has an anti-nociceptive effect related to a reduction in neuronal excitability and voltage-gated Na(+) channels (NaV) inhibition in peripheral neurons. However, the detailed mechanisms of carvacrol-induced inhibition of neuronal NaV remain elusive. This study explores the interaction between carvacrol and NaV in isolated dorsal root ganglia neurons. Carvacrol reduced the total voltage-gated Na(+) current and tetrodotoxin-resistant (TTX-R) Na(+) current component in a concentration-dependent manner. Carvacrol accelerates current inactivation and induced a negative-shift in voltage-dependence of steady-state fast inactivation in total and TTX-R Na(+) current. Furthermore, carvacrol slowed the recovery from inactivation. Carvacrol provoked a leftward shift in both the voltage-dependence of steady-state inactivation and activation of the TTX-R Na(+) current component. In addition, carvacrol-induced inhibition of TTX-R Na(+) current was enhanced by an increase in stimulation frequency and when neurons were pre-conditioned with long depolarization pulse (5s at -50 mV). Taken all results together, we herein demonstrated that carvacrol affects NaV gating properties. The present findings would help to explain the mechanisms underlying the analgesic activity of carvacrol.
authors: Laboratório de Membranas Excitáveis e Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors: Humberto Cavalcante
authors: HC
authors: Joca
authors: Laboratório de Membranas Excitáveis e Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Laboratório de Eletrofisiologia, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, CE, Brazil.
authors: Daiana Cardoso Oliveira
authors: DC
authors: Vieira
authors: Laboratório de Biotecnologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
authors: Aliny Perreira
authors: AP
authors: Vasconcelos
authors: Laboratório de Biotecnologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
authors: Demetrius Antônio Machado
authors: DA
authors: Araújo
authors: Laboratório de Membranas Excitáveis e Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: jcruz@icb.ufmg.br.
authors: Jader Santos
authors: JS
authors: Cruz
mesh_terms: D000818:Animals; D000081007:Cymenes; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology*; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000633:toxicity
chemical_list: D000081007:Cymenes; D039821:Monoterpenes; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568319:Scn10a protein, rat; D013779:Tetrodotoxin; C073316:carvacrol
keywords: Carvacrol; Dorsal root ganglia; Peripheral neurons; Tetrodotoxin-resistant sodium current; Voltage-gated sodium channels