Thyrotropin-releasing-hormone (TRH) and its physiological metabolite TRH-OH inhibit Na+ channel activity in mammalian septal neurons.
The interaction of thyrotropin-releasing hormone (TRH) and its physiological metabolite TRH-OH with Na+ channels was studied in enzymatically dissociated guinea pig septal neurons by using the whole-cell variant of the patch-clamp technique. In about 60% of the cells tested, the neuropeptides at concentrations between 0.01 and 2.5 microM produced a dose-dependent reversible attenuation of Na+ currents. With 2 microM TRH-OH, peak Na+ current amplitude was reduced by 20-50% (27 +/- 8%, mean +/- SD; n = 16), whereas at the same concentration TRH was approximately half as effective as TRH-OH. In the presence of the tripeptides, the voltage-dependent parameter of the Na+ current were unaltered. TRH-induced reduction of Na+ current amplitude was transient and recovered almost completely during maintained exposure to the peptides. In addition, the response to either TRH-OH or TRH decreased with repeated treatment. Our results demonstrate that neuronal Na+ channels can be modulated by naturally occurring neuropeptides.
López-Barneo
J
J
Departamento de Fisiología y Biofísica, Facultad de Medicina, Avenida Sánchez Pizjuán, Spain.
Castellano
A
A
Toledo-Aral
J
J
D000818:Animals; D001921:Brain / Q000502:physiology*; D004553:Electric Conductivity; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
D015221:Potassium Channels; D015222:Sodium Channels; C020271:thyrotropin-releasing hormone, deamido-; D013973:Thyrotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid