title: Metergoline inhibits the neuronal Nav1.2 voltage-dependent Na(+) channels expressed in Xenopus oocytes.
abstract: OBJECTIVE
  Metergoline is an ergot-derived psychoactive drug that acts as a ligand for serotonin and dopamine receptors. The aim of this study was to investigate the regulatory effects of metergoline on the neuronal Nav1.2 voltage-dependent Na(+) channels in vitro.
  
  
  METHODS
  Xenopus oocytes were injected with cRNAs encoding rat brain Nav1.2 α and β1 subunits. Voltage-activated Na(+) currents were recorded using two-electrode voltage clamp technique. Drugs were applied though perfusion.
  
  
  RESULTS
  Both metergoline and lidocaine reversibly and concentration-dependently inhibited the peak of Na(+) currents with IC50 values of 3.6 ± 4.2 and 916.9 ± 98.8 μmol/L, respectively. Metergoline (3 μmol/L) caused a 6.8 ± 1.2 mV depolarizing shift of the steady-state activation curve of the Na(+) currents, and did not alter the inactivation curve. In contrast, lidocaine (3 μmol/L) caused a 12.7 ± 1.2 mV hyperpolarizing shift of the inactivation curve of the Na(+) currents without changing the steady-state activation curve. Both metergoline and lidocaine produced tonic and use-dependent inhibition on the peak of Na(+) currents.
  
  
  CONCLUSIONS
  Metergoline exerts potent inhibition on the activity of neuronal Nav1.2 channels, which may contribute to its actions on the central nervous system.
authors.affiliation: 1] Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea [2] Present address: Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Minkyu
authors.initials: M
authors.lastname: Shin
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Moochang
authors.initials: M
authors.lastname: Hong
authors.affiliation: College of Veterinary Medicine, Konkuk University, Seoul 130-701, Republic of Korea.
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Hyunsu
authors.initials: H
authors.lastname: Bae
mesh_terms: D000818:Animals; D015870:Gene Expression; D008711:Metergoline / Q000494:pharmacology*; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; D061567:Voltage-Gated Sodium Channel Blockers; D008711:Metergoline