AJP - Gastrointestinal and Liver Physiology, Vol 263, Issue 4 508-G517, Copyright © 1992 by American Physiological Society

ARTICLES

Effects of thyrotropin-releasing hormone on neurons in rat dorsal motor nucleus of the vagus, in vitro

R. A. Travagli, R. A. Gillis and S. Vicini
Fidia Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington, DC 20007.

We sought to characterize the excitatory effect of thyrotropin-releasing hormone (TRH) in dorsal motor nucleus of the vagus (DMV) motoneurons by using the patch-clamp technique in rat brain stem slices. In our initial studies we used the cell-attached recording configuration using concentrations of TRH from 1 to 30 microM. Exposure of DMV motoneurons to TRH resulted in a concentration-related increase in spontaneously occurring action potential firing rate. This was observed in 63 of 85 DMV neurons (75%) tested and was unrelated to their location rostral or caudal to the obex. Invariably, desensitization occurred to the excitatory effect of TRH. Subsequent experiments using whole cell recordings in the current-clamp mode confirmed that TRH excites DMV neurons located both rostral and caudal to the obex. In the current-clamp configuration, TRH produced depolarization; i.e., 30 microM TRH elicited a depolarization of 8.7 +/- 3.2 mV (P < 0.05, n = 7). Studies using whole cell current recordings in voltage-clamp mode indicated that TRH in a concentration-dependent manner produces a small inward current that is associated with a decrease in the input resistance of -42.5 +/- 15.6 M omega (TRH 30 microM). TRH-induced inward current was also present under conditions of inhibition of synaptic transmission (i.e., in the presence of tetrodotoxin and cobalt). We also found that TRH reduced in a concentration-dependent manner both the fast transient A-type K+ current (IA) and the Ca(2+)-dependent afterhyperpolarizing current (IAHP). Using the extracellular recording technique in the cell-attached configuration, we investigated whether any part of TRH-induced increase in firing rate was due to an increase in the synaptic release of L-glutamate or acetylcholine. Prior exposure of DMV neurons to either kynurenic acid or to atropine did not antagonize any of the excitatory effect of TRH. Finally, we observed that addition of 30 microM TRH to the perfusing solution produced an increase in spontaneously occurring excitatory postsynaptic currents (EPSCs). This occurred without any change in the amplitude of EPSCs. These results indicated that TRH-induced increase in firing of DMV neurons is due to direct postsynaptic effects to activate an inward cationic current and to counteract IA and IAHP, as well as a presynaptic effect to increase the frequency of EPSCs.

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