2 CONDUCTANCES MEDIATE THYROTROPIN-RELEASING-HORMONE-INDUCED DEPOLARIZATION OF NEONATAL RAT SPINAL PREGANGLIONIC AND LATERAL HORN NEURONS

Thyrotropin-releasing hormone (TRH) has been recognized as a neuromodu lator in several CNS regions, including the thoracolumbar spinal cord where an influence on cardiovascular autonomic function has been propo sed. To identify the cellular mechanisms involved in the latter, whole cell patch-clamp recordings were obtained from 52 thoracolumbar later al horn cells, including 17 sympathetic preganglionic neurons (SPNs), in spinal cord slices from neonatal rat(11-21 days). Under current cla mp, bath applications of TRW (1-20 mu M) induced a slowly rising and p rolonged membrane depolarization in eight of nine cells tested. Under voltage clamp (holding potential -65 mV), 33 of 37 tested cells displa yed a TRH-induced, tetrodotoxin-resistant inward current that was asso ciated with either a reduction or an increase in membrane ion conducta nces. Current-voltage (I-V) relationships in 28 cells suggested two co nductances. In 9 cells the current reversed at about -107 mV; in 10 ce lls the I-V lines remained parallel, whereas in 9 cells the current re versed at around -40 mV. In three of three cells, addition of 2 mM bar ium was associated with an inward current, and the TRH-induced inward current was also suppressed, suggesting the presence of a resting bari um-and TRI-I-sensitive potassium conductance. A residual barium-insens itive conductance was seen to reverse near -40 mV. Intracellular dialy sis with guanosine 5'-o-(3-thiotriphosphate) significantly enhanced th e duration of the TRH effect, indicating that protein activation parti cipates in the TRH response. These observations not only reveal a dire ct, G-protein-mediated depolarizing action of TRH on neonatal rat SPNs and lateral horn cells but also imply that two separate conductances may be involved in the TRH responses in some neurons.