title: Mechanisms underlying excitatory effects of thyrotropin-releasing hormone on rat hypoglossal motoneurons in vitro.
abstract: 1. The hypoglossal motor nucleus contains binding sites for the neuropeptide thyrotropin-releasing hormone (TRH) and is innervated by TRH-containing fibers. Although excitatory effects of TRH on hypoglossal motoneurons (HMs) have been described, the ionic mechanisms by which TRH exerts such effects have not been fully elucidated. Therefore, we investigated the effects of TRH on HMs in transverse slices of rat brainstem with intracellular recording techniques. 2. TRH was applied by perfusion (0.1-10 microM) or by pressure ejection (1.0 microM), while HMs were recorded in current or voltage clamp. In all cells tested, TRH caused a depolarization and/or the development of an inward current. These effects were fully reversible, dose dependent, and showed only modest desensitization with long applications. In addition, although TRH increased synaptic activity in many cells, the depolarizing response to TRH was maintained in tetrodotoxin (0.5-1.0 microM)-containing or in a nominally Ca(2+)-free perfusate containing 2 mM Mn2+. Thus TRH acts directly on HMs to cause the depolarization. 3. Hyperpolarizing current (or voltage) steps superimposed on the TRH-induced depolarization (or inward current) revealed a decreased input conductance. Extrapolated instantaneous current-voltage relationships obtained before and at the peak of the response to TRH intersected (i.e., reversed) at -101 mV, negative to the expected K+ equilibrium potential (EK). When extracellular [K+] was raised from 3 to 12 mM, the reversal potential was shifted in the depolarizing direction and the magnitude of the TRH-induced depolarization was diminished. Moreover, the TRH response was enhanced in size from depolarized potentials (i.e., further from EK). Taken together, these results indicate that TRH depolarizes HMs, in part, by decreasing a resting K+ conductance. 4. Similar to TRH, bath-application of 2 mM Ba2+ caused a depolarization associated with decreased conductance, suggesting that Ba2+ also blocks a resting K+ conductance. The Ba(2+)-sensitive and TRH-sensitive resting K+ conductances are apparently identical; in the presence of Ba2+, the customary TRH-induced decrease in conductance was occluded. 5. It is noteworthy that the TRH-induced inward current (ITRH), although diminished, was not entirely blocked by Ba2+. This second Ba(2+)-insensitive component of ITRH was not associated with a measurable change in input conductance. It was especially evident during current-clamp recordings, when the diminutive TRH-induced current was still capable of causing a substantial depolarization. The ionic basis of the residual TRH-induced inward current remains to be determined. 6. We investigated the functional consequences of these mechanisms of action of TRH on spike firing behavior of HMs.(ABSTRACT TRUNCATED AT 400 WORDS)
authors: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195.
authors: D A
authors: DA
authors: Bayliss
authors: F
authors: F
authors: Viana
authors: A J
authors: AJ
authors: Berger
mesh_terms: D000818:Animals; D001464:Barium / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D005260:Female; D007002:Hypoglossal Nerve / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
chemical_list: D007202:Indicators and Reagents; D015221:Potassium Channels; D001464:Barium; D013779:Tetrodotoxin; D013973:Thyrotropin-Releasing Hormone