Effects of thyrotropin-releasing hormone on rat motoneurons are mediated by G proteins.
Numerous transmitter receptors are linked via GTP-binding proteins (G proteins) to membrane phosphoinositide metabolism by phospholipase C (PLC) and generation of second messengers such as activated protein kinase C (PKC), inositol trisphosphate (IP3) and/or elevations in intracellular calcium. In many cases, these same receptors also inhibit a resting ('leak') potassium current (IK(L)), thereby depolarizing neurons. It is unclear if activation of this PLC pathway mediates inhibition of IK(L) by neurotransmitter receptors. Therefore, we tested the contribution of this pathway to the TRH-induced inhibition of IK(L) in rat hypoglossal motoneurons (HMs) using conventional intracellular recording in brainstem slices. When HMs were recorded with electrodes containing 3 M KCl or 30 mM GTP (in KCl), TRH induced a depolarization that recovered quickly (within 8-10 min) and could be repeated with only modest tachyphylaxis (< 20%). However, with electrodes containing the non-hydrolyzable G protein activator, GTP gamma S (10 mM), the TRH-induced depolarization was long lasting (up to 1 h); with electrodes containing the G protein inhibitor, GDP beta S (20 mM) the tachyphylaxis with repeated TRH application was exaggerated (approximately 60%). Activation of PKC by phorbol dibutyrate (10 microM in perfusate) neither mimicked nor occluded the effects of TRH. There were no effects on membrane potential, input resistance (RN) or the response to TRH in HMs during long recordings with electrodes containing high concentrations of IP3 (60 mM).(ABSTRACT TRUNCATED AT 250 WORDS)
Bayliss
D A
DA
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195, USA.
Viana
F
F
Berger
A J
AJ
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D001933:Brain Stem / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate; D015221:Potassium Channels / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*
D015221:Potassium Channels; D018025:Receptors, Thyrotropin-Releasing Hormone; D015240:Phorbol 12,13-Dibutyrate; D013973:Thyrotropin-Releasing Hormone; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D002118:Calcium