Two 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 neuromodulator in several CNS regions, including the thoracolumbar spinal cord where an influence on cardiovascular autonomic function has been proposed. To identify the cellular mechanisms involved in the latter, whole cell patch-clamp recordings were obtained from 52 thoracolumbar lateral horn cells, including 17 sympathetic preganglionic neurons (SPNs), in spinal cord slices from neonatal rat (11-21 days). Under current clamp, bath applications of TRH (1-20 microM) induced a slowly rising and prolonged membrane depolarization in eight of nine cells tested. Under voltage clamp (holding potential -65 mV), 33 of 37 tested cells displayed a TRH-induced, tetrodotoxin-resistant inward current that was associated with either a reduction or an increase in membrane ion conductances. Current-voltage (I-V) relationships in 28 cells suggested two conductances. In 9 cells the current reversed at about -107 mV; in 10 cells the I-V lines remained parallel, whereas in 9 cells the current reversed at around -40 mV. In three of three cells, addition of 2 mM barium was associated with an inward current, and the TRH-induced inward current was also suppressed, suggesting the presence of a resting barium- and TRH-sensitive potassium conductance. A residual barium-insensitive conductance was seen to reverse near -40 mV. Intracellular dialysis with guanosine 5'-o-(3-thiotriphosphate) significantly enhanced the duration of the TRH effect, indicating that G protein activation participates in the TRH response. These observations not only reveal a direct, 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.
Kolaj
M
M
Neuroscience Unit, Loeb Research Institute, Ottawa Civic Hospital and University of Ottawa, Ontario, Canada.
Shefchyk
S J
SJ
Renaud
L P
LP
D000818:Animals; D005727:Ganglia, Spinal / Q000166:cytology* / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D007473:Ion Channels; D009467:Neuromuscular Depolarizing Agents; D013973:Thyrotropin-Releasing Hormone