TRH regulates action potential shape in cerebral cortex pyramidal neurons.
Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region.
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), AP 70250, México, D.F. 04510, México; Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
Víctor
V
Rodríguez-Molina
Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
Javier
J
Patiño
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Ave. Universidad 2001, Chamilpa, Cuernavaca, Morelos 62210, México.
Yamili
Y
Vargas
Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría, Ramón de la Fuente Muñíz, México D.F., México.
Edith
E
Sánchez-Jaramillo
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Ave. Universidad 2001, Chamilpa, Cuernavaca, Morelos 62210, México.
Patricia
P
Joseph-Bravo
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Ave. Universidad 2001, Chamilpa, Cuernavaca, Morelos 62210, México. Electronic address: charli@ibt.unam.mx.
Jean-Louis
JL
Charli
D000200:Action Potentials / Q000187:drug effects*; D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000235:genetics; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D066191:Sensorimotor Cortex / Q000166:cytology*; D013873:Thionucleotides / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
D012333:RNA, Messenger; C493466:Slc17a7 protein, rat; D013873:Thionucleotides; D050598:Vesicular Glutamate Transport Protein 1; D006153:Guanosine Diphosphate; D013973:Thyrotropin-Releasing Hormone; C023427:guanosine 5'-O-(2-thiodiphosphate); D000626:Aminopeptidases; C023166:pyroglutamyl-peptidase II; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D011761:Pyrrolidonecarboxylic Acid
Action potential; Cortical pyramidal neuron; Cortical slices; Pyroglutamyl peptidase II; TRH