A study of the barium-sensitive and -insensitive components of the action of thyrotropin-releasing hormone on lumbar motoneurons of the rat isolated spinal cord.
The electrophysiological action of thyrotropin-releasing hormone (TRH) on rat spinal motoneurons was studied in vitro using single-electrode voltage- and current-clamp techniques. In current-clamp conditions TRH elicited a slowly developing depolarization, associated with a large input resistance increase and sustained neuronal firing; the primary metabolites of TRH were ineffective. Under voltage-clamp conditions in the presence of tetrodotoxin, TRH evoked a large inward current (ITRH; peaking at approximately -40 mV) associated with a large input conductance fall. Only 44% of cells displayed ITRH reversal; when the chord conductance values of these cells were plotted against membrane potential, a bell-shaped relation occurred, indicating voltage-dependent block by TRH of a persistent conductance active over a wide range of membrane potentials. ITRH reversal values were shifted to more positive levels in high K+ solution in Nernstian fashion; hence a large proportion of the TRH response is suggested to be mediated by the block of a K+ conductance (IK(T)). IK(T) (and its voltage-dependent block by TRH) was resistant to certain K+ channel antagonists (tetraethylammonium, Cs+, 4-aminopyridine or apamin), but was depressed by Ba2+. The Ba(2+)-resistant fraction of ITRH was attenuated by Cd2+, Mn2+ or Co2+, indicating that it probably involved a Ca(2+)-sensitive inward current. Concomitant application of Ba2+ and Cd2+ induced a near-total block of the response to TRH. It is suggested that suppression of IK(T), associated with the onset of a Ca(2+)-sensitive current, can explain the excitatory effect of TRH on rat spinal motoneurons.
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Biophysics Sector, International School for Advanced Studies (S.I.S.S.A.), Trieste, Italy.
Nistri
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D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001030:Apamin / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology*; D002413:Cations, Divalent; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D002413:Cations, Divalent; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D002586:Cesium; D001030:Apamin; D001464:Barium; D013779:Tetrodotoxin; D013973:Thyrotropin-Releasing Hormone; D019789:Tetraethylammonium; D015761:4-Aminopyridine