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 (I_TRH; peaking at approximately –40 mV) associated with a large input conductance fall. Only 44% of cells displayed I_TRH 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. I_TRH 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 (I_K(T)). I_K(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 Ba²⁺-resistant fraction of I_TRH was attenuated by Cd²⁺, Mn²⁺ or Co²⁺, indicating that it probably involved a Ca²⁺-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 I_K(T), associated with the onset of a Ca²⁺-sensitive current, can explain the excitatory effect of TRH on rat spinal motoneurons.