A STUDY OF THE BARIUM-SENSITIVE AND BARIUM-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 TR H 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 (I(TR H); peaking at approximately -40 mV) associated with a large input con ductance fall. Only 44% of cells displayed I(TRH) reversal; when the c hord conductance values of these cells were plotted against membrane p otential, a bell-shaped relation occurred, indicating voltage-dependen t block by TRH of a persistent conductance active over a wide range of membrane potentials. I(TRH) reversal values were shifted to more posi tive levels in high K+ solution in Nernstian fashion; hence a large pr oportion of the TRH response is suggested to be mediated by the block of a K+ conductance (I(K(T))). I(K(T)) (and its voltage-dependent bloc k by TRH) was resistant to certain K+ channel antagonists (tetraethyla mmonium, Cs+, 4-aminopyridine or apamin), but was depressed by Ba2+. T he Ba2+-resistant fraction of I(TRH) was attenuated by Cd2+, Mn2+ or C o2+, indicating that it probably involved a Ca2+-sensitive inward curr ent. Concomitant application of Ba2+ and Cd2+ induced a near-total blo ck of the response to TRH. It is suggested that suppression of I(K(T)) , associated with the onset of a Ca2+-sensitive current, can explain t he excitatory effect of TRH on rat spinal motoneurons.