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.