Division of Gastroenterology and Department of Physiology, University of Michigan Medical Center, Ann Arbor, Michigan 48109
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ABSTRACT |
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Using whole cell patch-clamp recordings, we investigated the effects of the GABAB receptor agonist baclofen in thin slices of rat brain stem containing identified gastric- or intestinal-projecting dorsal motor nucleus of the vagus (DMV) neurons. Perfusion with baclofen (0.1-100 µM) induced a concentration-dependent outward current (EC50, 3 µM) in 54% of DMV neurons with no apparent differences between gastric- and intestinal-projecting neurons. The outward current was attenuated by pretreatment with the selective GABAB antagonists saclofen and 2-hydroxysaclofen, but not by the synaptic blocker TTX, indicating a direct effect at GABAB receptors on DMV neurons. Using the selective ion channel blockers barium, nifedipine, and apamin, we showed that the outward current was due to effects on potassium and calcium currents as well as calcium-dependent potassium currents. The calcium-mediated components of the outward current were more prominent in intestinal-projecting neurons than in gastric-projecting neurons. These data indicate that although baclofen inhibits both intestinal- and gastric-projecting neurons in the rat DMV, its mechanism of action differs among the neuronal subpopulations.
brain stem; electrophysiology; gastrointestinal
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INTRODUCTION |
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THE DORSAL MOTOR NUCLEUS OF the vagus (DMV) contains the neurons that provide the parasympathetic efferent outflow to the subdiaphragmatic viscera (12, 22). Afferent neurons innervating the gastrointestinal tract project to, and terminate within, the DMV either directly or via interneurons in the nucleus of the solitary tract (NTS) (2, 25, 26, 30). DMV neurons are under inhibitory control from GABAergic neurons of the NTS (31, 32). The inhibitory actions of GABA on DMV neurons are thought to be exerted primarily by fast ionic currents mediated via GABAA receptor activation (32). Although autoradiographic studies (1, 6, 20) have demonstrated that GABAB receptors also are located throughout the dorsal vagal complex (DVC), i.e., the DMV plus the NTS, to date there is no evidence to suggest that functional GABAB receptors exist on DMV neuronal membranes.
Functional in vivo studies have shown that subcutaneous or intracerebroventricular application of the GABAB receptor agonist baclofen increases gastric and intestinal motility (3, 10) as well as initiating vagal discharges similar to those obtained on stimulation of gastric secretion (13). These apparently contradictory results can be explained if activation of GABAB receptors involves separate subpopulations of DVC neurons. One population would comprise excitatory DMV neurons that do not have GABAB receptors on their membrane but rather receive an inhibitory input, most likely from NTS, which is inhibited by activation of GABAB receptors. The disinhibition of these DMV neurons would result in an excitatory effect such as increase in gastric motility. Indeed, electrophysiological studies have shown that baclofen acts directly on NTS neurons to produce a membrane hyperpolarization (7), as well as indirectly to inhibit synaptic transmission from vagal afferents (7, 23). Another DMV neuronal population, most likely participating in inhibitory control of gastric functions, would have GABAB receptors on the membrane but would not receive inhibitory inputs containing GABAB receptors on the presynaptic membrane. The inhibition of these DMV neurons resulting from activation of GABAB receptors would reduce their inhibitory influence, causing an increase in gastric pressure. Indeed, Andrews et al. (3) hypothesized that the observed atropine-insensitive increase in gastric pressure obtained by baclofen was probably mediated via an action at a central site to reduce the tonic vagal drive to nonadrenergic noncholinergic (NANC) inhibitory neurons.
The cellular mechanisms coupled to postsynaptic GABAB receptor activation are well documented (5, 11, 14, 17, 27, 34, 35). The mechanisms comprise activation of potassium- as well as inhibition of voltage-dependent calcium conductances and adenylate cyclases.
We (8, 9) have shown recently that the DMV is composed of heterogeneous neuronal populations in terms of both membrane as well as pharmacological properties. These populations can be further distinguished based on their peripheral targets.
The aims of this study were to investigate 1) whether GABAB receptors are functionally present on the DMV membrane, and if so, 2) what the mechanism of action of the GABAB agonist baclofen is on the DMV membrane, and 3) whether there are differences in the responses of DMV neurons identified as per their peripheral projections.
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METHODS |
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Retrograde tracing. The retrograde tracer DiI was applied to discrete gastrointestinal regions in 12-day-old Sprague-Dawley rat pups of either sex, as described previously (8). Briefly, rats were anesthetized deeply with a 6% solution of halothane in accordance with the guidelines of the Animal Care and Use Committee of the University of Michigan Medical Center (Ann Arbor, MI). The depth of anesthesia (abolition of the foot pinch withdrawal reflex) was monitored before and during surgery. The abdominal area was shaved and cleaned with alcohol before a laparotomy was performed. Crystals of DiI were applied to either the major curvature of the gastric fundus or corpus, the antrum/pylorus, the duodenum (the antimesenteric surface at the level of the hepatic and pancreaticoduodenal arteries), or the minor curvature of the cecum (at the level of the ileocecal junction). The application site was embedded in a fast-hardening epoxy resin before the entire surgical area was washed with warm, sterile saline. The wound was closed with 4-0 sutures, and the animal was allowed to recover for 10-15 days.
Electrophysiology. The method used for tissue slice preparation was as described previously (32). Briefly, rats were anesthetized deeply (halothane bubbled with air) before being killed through severing of the major blood vessels in the chest. The brain stem was removed and placed in chilled (4°C) oxygenated Krebs solution (see below for composition). Using a vibratome, we cut six to eight coronal slices containing the DMV. Slices were stored in oxygenated Krebs solution at 32°C for at least 1 h before use. A slice was then placed on a custom-made perfusion chamber (vol 500 µl) and maintained at 35°C by continual perfusion with warmed oxygenated Krebs solution at a rate of 2.5 ml/min.
Retrogradely labeled neurons were identified before electrophysiological recording using a Nikon E600FS microscope fitted with DIC (Nomarski) optics and tetramethylrhodamine isothiocyanate epifluorescent filters. The brief periods of illumination required to detect the fluorescent neurons have not been observed to cause any damage (16, 21). Once a labeled neuron was identified, electrophysiological recordings were made under bright-field illumination. Whole cell recordings were made only from retrogradely labeled gastrointestinal-projecting neurons using patch pipettes filled with potassium gluconate solution of resistance 3-8 MDrug application.
Drugs were applied to the bath via a series of manually operated
valves. Baclofen (10 µM) was applied to all neurons to ascertain whether or not it had any effect per se before the appropriate experiment was continued. When voltage clamped at 50 mV, a minimum peak current of 20 pA had to be induced by baclofen (10 µM) to classify the neuron as responsive. Drug effects were assessed with each
neuron acting as its own control, i.e., the results obtained after
administration of a receptor antagonist or channel blocker were
compared with those obtained before administration using the paired
t-test. Drugs were applied in concentrations shown
previously to be effective. Results are expressed as means ± SE
with significance defined as P < 0.05. To minimize
sampling biases, only one experiment was conducted per each brain stem slice and only one experiment of each type was conducted per animal.
Chemicals and solutions. Krebs solution was composed of (in mM): 126 NaCl, 25 NaHCO3, 2.5 KCl, 1.2 MgCl2, 2.4 CaCl2, 1.2 NaH2PO4, and 11 dextrose, maintained at pH 7.4 by bubbling with 95%O2-5% CO2. Intracellular solution consisted of (in mM): 128 potassium gluconate, 10 KCl, 0.3 CaCl2, 1 MgCl2, 1 HEPES, 1 EGTA, 2 ATP, and 0.25 GTP, adjusted to pH 7.35 with KOH. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiIC18(3); DiI] was purchased from Molecular Probes (Eugene, OR). R(+) Baclofen and 2-hydroxysaclofen were purchased from RBI (Natick, MA). Halothane and all other drugs and chemicals were purchased from Sigma Chemical (St. Louis, MO).
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RESULTS |
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Baclofen induces outward current in subpopulation of
DMV neurons.
The effects of the GABAB receptor agonist baclofen were
assessed in 394 gastrointestinal-projecting neurons of the DMV (211 gastric projecting and 187 intestinal projecting). Baclofen induced a
concentration-dependent (0.1-100 µM) outward current in 211 (i.e., 54%) of these neurons. No differences were observed in the
magnitude of the baclofen-induced current among the gastric and
intestinal groups; data were thus pooled and provided an estimated EC50 of 3 µM (Fig. 1). The
percentage of responsive neurons did not differ between the gastric-
and intestinal-projecting neurons; in fact, 112 of 211 gastric-projecting neurons (i.e., 53%) and 99 of 187 intestinal-projecting neurons (i.e., 54%) responded to perfusion with
10 µM baclofen. Similarly, the distribution of the magnitude of the
response to 10 µM baclofen did not differ between gastric- and
intestinal-projecting neurons (Fig. 1).
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Baclofen effect involves several ionic conductances. The effects of the nonselective potassium channel blocker barium (2 mM) on the outward current induced by baclofen (10 µM) were assessed in 14 neurons (7 gastric and 7 intestinal). The baclofen-induced current was reduced from 66 ± 14 pA in control conditions to 25 ± 5 pA in the presence of barium, i.e., 41 ± 3.6% of control (P < 0.05; data not shown, however, see Fig. 3). No significant differences were observed in the actions of barium between gastric- and intestinal-projecting neurons. In detail, barium reduced the baclofen-induced current from 73 ± 24 to 25 ± 7 pA in gastric-projecting neurons and from 60 ± 17 to 24 ± 8 pA in intestinal-projecting neurons, i.e., 41 ± 5% and 41 ± 6% of control in gastric- and intestinal-projecting neurons, respectively.
The effects of the L-type calcium channel blocker nifedipine (3 µM) on the baclofen (10 µM)-induced outward current were assessed in 34 neurons (19 gastric and 15 intestinal). The baclofen-induced current was reduced from 76 ± 8.9 pA under control conditions to 40 ± 4.7 pA in the presence of nifedipine, i.e., 53 ± 2.4% of control (P < 0.05; data not shown, however, see Fig. 3). Significant differences were uncovered, however, in the magnitude of this reduction between gastric- and intestinal-projecting neurons. In gastric-projecting neurons, nifedipine reduced the baclofen-induced current from 85 ± 14 to 47 ± 7 pA, i.e., 58 ± 3% of control, whereas in intestinal-projecting neurons, nifedipine reduced the baclofen-induced current from 66 ± 9 to 32 ± 6 pA, i.e., 47 ± 3% of control (P < 0.05). The involvement of both potassium and calcium conductances in mediating the actions of baclofen was confirmed by assessing the reversal potential for the baclofen-induced outward current in the absence and presence of both channel blockers. The baclofen-induced current reversed at approximately
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DISCUSSION |
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The present study provides the first direct evidence that functional GABAB receptors are located on the membrane of DMV neurons. In fact, the GABAB agonist baclofen evoked a concentration-dependent outward (inhibitory) current in a subpopulation of gastrointestinal-projecting DMV neurons via direct activation of postsynaptic GABAB receptors. The baclofen-induced outward current was mediated by several ionic conductances, namely a potassium conductance, a calcium conductance, and a calcium-dependent potassium conductance.
Although the proportion of neurons responding to baclofen and the magnitude of response were similar in gastric- and intestinal-projecting neurons, the action of baclofen, however, appeared to differ. In fact, in intestinal-projecting neurons, the calcium-mediated components of the outward current appeared to exert a more prominent role than in gastric-projecting neurons. Such differential effects provide further evidence for the nonuniformity of gastrointestinal-projecting DMV neurons (8, 9).
In both gastric- and intestinal-projecting neurons, ~60% of the baclofen-induced response was mediated via activation of a barium-sensitive potassium conductance. Gastric- and intestinal-projecting neurons differed, however, in the proportion of the baclofen-induced response attributable to an effect on the inward L-type calcium conductance (42% vs. 53%, respectively; see nifedipine experiments), in the proportion of the response attributable to an effect on the apamin-sensitive calcium-dependent potassium (SK) conductance (32% vs. 48%, respectively; see apamin experiments), and in the contribution of the L-type calcium conductance to the effect on the SK conductance (100% vs. 84%, respectively; see nifedipine and apamin experiments).
Baclofen has been reported previously (14, 18, 35) to inhibit L-, N- and P/Q-type calcium channels, depending on the neuronal type investigated. For example, in rat hippocampus inhibitory neurons, baclofen inhibits L-, N- and P/Q-type calcium channels (18), whereas in rat supraoptic nucleus neurons, baclofen inhibits only N- and P/Q-type channels (14) and in cerebellar granule cells, baclofen inhibits L-type channels (35). Although the effects of baclofen on calcium channels other than the L-type channel were not investigated in detail in the present study, it would appear that the major proportion of the baclofen-induced inhibition of calcium channels in vagal motoneurons is mediated via inhibition of L-type calcium channels. Indeed, the combination of nifedipine and barium almost completely abolished the baclofen-induced outward current. However, after pretreatment with nifedipine alone, a small proportion of the baclofen-induced current was further inhibited by perfusion of nifedipine in combination with the nonselective calcium channel blocker cadmium. These data indicate that calcium channels other than the L-type are also affected, although such channels play a minor role in the overall baclofen response.
The present study seems to indicate differences between gastric- and intestinal-projecting neurons with regard to the source of calcium necessary to activate the apamin-sensitive calcium-dependent potassium current. In fact, the baclofen current obtained in the presence of nifedipine compared with nifedipine in combination with a supramaximal concentration of apamin (24) did not differ in gastric-projecting neurons. When the same cocktail of antagonists was tested in intestinal-projecting neurons, however, a further 10% inhibition in the baclofen-induced current was observed after pretreatment with nifedipine and apamin. These data would suggest that the apamin-sensitive current in gastric-projecting neurons is fully activated by calcium entry via L-type channels, whereas in intestinal neurons sources other than the L-type calcium channels also play a role. Indeed, a different complement of voltage-dependent calcium currents has been shown to be present in rat vagal motoneurons (24, 28), although their selective localization has not been investigated.
Although elucidating the sources of calcium necessary to activate calcium-dependent potassium currents is beyond the scope of the present study, the observed differences between gastric- and intestinal-projecting neurons are a further indication of the distinct basic characteristics of DMV neurons projecting to separate areas of the gastrointestinal tract (8, 9).
Activation of central GABAB receptors results in several gastrointestinal effects, such as increase in gastric and intestinal motility (3, 10), increase in gastric acid secretion (13), increase in lower esophageal sphincter (LES) pressure (4), and decrease of glutamate-induced LES relaxation (1). A similar dichotomy, i.e., both excitatory and inhibitory central effects of baclofen, has also been seen in a recent clinical study (19). In their work on healthy volunteers, Lidums and colleagues (19) showed that baclofen decreased the rate of transient LES relaxations, but at the same time, increased basal LES pressure, probably via a vagally mediated pathway.
To the best of our knowledge, no in vivo studies in animal models have been performed in which baclofen has been microinjected directly in the DVC while gastrointestinal effects were monitored. However, convincing evidence (1, 3, 4, 10, 13) points toward the DVC as the central site of action of baclofen on gastrointestinal function.
In an in vivo study using a ferret model, Andrews and colleagues (3) administered baclofen subcutaneously and observed an increase in gastric pressure as well as an increase in the amplitude of rhythmic contractions. Both effects were abolished by vagotomy (3). In the same study, Andrews et al. (3) reported that, in the presence of cholinergic and sympathetic blockade, the actions of baclofen were restricted to an increase in gastric corpus pressure. Such actions can be explained if one considers baclofen to have dual central effects: 1) an increase in vagal excitatory cholinergic drive to mediate the increase in rhythmic contractions and 2) a decrease in tonic vagal drive to NANC inhibitory neurons to mediate the increase in gastric pressure (3). At the cellular level, then, such an apparent contradiction can be resolved if one assumes that the increase in vagal cholinergic drive occurs as a result of the vagal disinhibition that follows blockade of GABAergic NTS neurons impinging on DMV. On the other hand, direct inhibition of DMV neurons by baclofen would result in the relief of inhibitory NANC drive to the stomach.
Indeed, electrophysiological studies have shown that baclofen acts directly on all NTS neurons to produce a membrane hyperpolarization (7), as well as indirectly to inhibit synaptic transmission from vagal afferents (7, 23). Such actions would relieve the tonic inhibition that the GABAergic NTS neurons exert over the DMV and lead to an increased vagal motor output (31). Similarly, the baclofen-mediated increase in gastric acid secretion (13) can be explained by an increase in vagal activity obtained by disinhibition of NTS GABAergic neurons.
In contrast, the present study has shown that activation of GABAB receptors by baclofen is also capable of inducing a direct outward current, or membrane hyperpolarization, in a subpopulation of DMV neurons. The direct inhibition by baclofen of DMV neurons, which, in our hypothesis, control inhibitory NANC intramural neurons, provides a cellular substrate to explain the atropine-insensitive increase in gastric corpus pressure (3) and the excitatory effects on the LES (1, 4).
In conclusion, we have shown that 1) GABAB receptors are functionally present on the membrane of a large percentage of DMV neurons, 2) activation of GABAB receptors by baclofen inhibits several ionic conductances, namely a potassium conductance, a calcium conductance, and a calcium-dependent potassium conductance; and 3) the action of baclofen appeared to differ between gastric- and intestinal-projecting neurons. In fact, in intestinal-projecting neurons, the calcium-mediated components of the outward current appeared to exert a more prominent role than in gastric-projecting neurons.
Perspectives. Our data, would then provide an explanation at the cellular level of the apparently contradictory (i.e., excitatory and inhibitory) effects of baclofen on vagal motor activity. In fact, the overall effect of brain stem GABAB receptor activation seems to be highly dependent on the neuronal circuit under study as well as the complement and activity of ionic conductances within the DMV gastrointestinal motoneurons. Future studies combining in vivo and in vitro experiments aimed at separating these circuits will be required to resolve the neurochemical phenotype and the membrane properties of the neurons involved in the effects of GABAB receptor activation in the dorsal vagal complex.
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ACKNOWLEDGEMENTS |
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Portions of this work have been presented previously in abstract form (33).
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FOOTNOTES |
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Address for reprint requests and other correspondence: R. A. Travagli, Dept. of Internal Medicine, Division of Gastroenterology, 3912 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0362 (E-mail:travagli{at}umich.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 28 September 2000; accepted in final form 14 January 2001.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Abrahams, TP,
Ekstrand J,
Hyland NP,
and
Hornby PJ.
Immunocytochemical localization of GABAB receptors in ferret dorsal vagal complex and functional role in control of lower esophageal sphincter pressure (Abstract).
Soc Neurosci Abstr
25:
940,
1999.
2.
Altschuler, SM,
Bao X,
Bieger D,
Hopkins DA,
and
Miselis RR.
Viscerotopic representation of the upper alimentary tract in the rat: sensory ganglia and nuclei of the solitary and spinal trigeminal tracts.
J Comp Neurol
283:
248-268,
1989[ISI][Medline].
3.
Andrews, PL,
Bingham S,
and
Wood KL.
Modulation of the vagal drive to the intramural cholinergic and non-cholinergic neurones in the ferret stomach by baclofen.
J Physiol (Lond)
388:
25-39,
1987[Abstract].
4.
Blackshaw, LA,
Smid SD,
O'Donnel TA,
and
Dent J.
GABAB receptor-mediated effects on vagal pathways to the lower oesophageal sphincter and heart.
Br J Pharmacol
130:
279-288,
2000
5.
Bowery, NG.
Metabotropic GABAB receptors.
Neurotransmissions
15:
3-18,
1999.
6.
Bowery, NG,
Hudson AL,
and
Price GW.
GABAA and GABAB receptor site distribution in the rat central nervous system.
Neuroscience
20:
365-383,
1987[ISI][Medline].
7.
Brooks, PA,
Glaum SR,
Miller RJ,
and
Spyer KM.
The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro.
J Physiol (Lond)
457:
115-129,
1992[Abstract].
8.
Browning, KN,
Renehan WE,
and
Travagli RA.
Electrophysiological and morphological heterogeneity of rat dorsal vagal neurones which project to specific areas of the gastrointestinal tract.
J Physiol (Lond)
517:
521-532,
1999
9.
Browning, KN,
and
Travagli RA.
Characterization of the in vitro effects of 5-hydroxytryptamine (5-HT) on identified neurones of the rat dorsal motor nucleus of the vagus (DMV).
Br J Pharmacol
128:
1307-1315,
1999
10.
Fargeas, MJ,
Fioramonti J,
and
Bueno L.
Central and peripheral action of GABAA and GABAB agonists on small intestine motility in rats.
Eur J Pharmacol
150:
163-169,
1988[ISI][Medline].
11.
Gage, PW.
Activation and modulation of neuronal K+ channels by GABA.
Trends Neurosci
15:
46-51,
1992[ISI][Medline].
12.
Gillis, RA,
Quest JA,
Pagani FD,
and
Norman WP.
Control centers in the central nervous system for regulating gastrointestinal motility.
In: Handbook of Physiology. The Gastrointestinal System. Motility and Circulation. Bethesda, MD: Am. Physiol. Soc, 1989, sect. 6, vol. I, pt. 1, chapt. 17, p. 621-683.
13.
Goto, Y,
Tache Y,
Debas H,
and
Novin D.
Gastric acid and vagus nerve response to GABA agonist baclofen.
Life Sci
36:
2471-2475,
1985[ISI][Medline].
14.
Harayama, N,
Shibuya I,
Tanaka K,
Kabashima N,
Ueta Y,
and
Yamashita H.
Inhibition of N- and P/Q type calcium channels by postsynaptic GABAB receptor activation in rat supraoptic neurones.
J Physiol (Lond)
509:
371-383,
1998
15.
Hille, B.
Ionic Channels of Excitable Membranes. Sunderland, MA: Sinauer, 1992.
16.
Honig, MG,
and
Hume RI.
DiI and DiO: versatile fluorescent dyes for neuronal labelling and pathway tracing.
Trends Neurosci
12:
333-341,
1989[ISI][Medline].
17.
Kaupmann, K,
Huggel K,
Heid J,
Flor PJ,
Bischoff S,
Mickel SJ,
McMaster G,
Angst C,
Bittiger H,
Froestl W,
and
Bettler B.
Expression cloning of GABAB receptors uncovers similarity to metabotropic glutamate receptors.
Nature
386:
239-246,
1997[ISI][Medline].
18.
Lambert, NA,
and
Wilson WA.
High-threshold Ca2+ currents in rat hippocampal interneurones and their selective inhibition by activation of GABAB receptors.
J Physiol (Lond)
492:
115-127,
1996[Abstract].
19.
Lidums, I,
Lehman A,
Checklin H,
Dent J,
and
Holloway RH.
Control of transient lower esophageal sphincter relaxation and reflux by the GABAB agonist baclofen in normal subjects.
Gastroenterology
118:
7-13,
2000[ISI][Medline].
20.
Mcdermott, BJ,
Ekstrand J,
and
Hornby PJ.
Immunocytochemical GABAB receptor staining in the hindbrain of rodents (Abstract).
Soc Neurosci Abstr
25:
940,
1999.
21.
Mendelowitz, D,
and
Kunze DL.
Identification and dissociation of cardiovascular neurons from the medulla for patch clamp analysis.
Neurosci Lett
132:
217-221,
1991[ISI][Medline].
22.
Pagani, FD,
Norman WP,
and
Gillis RA.
Medullary parasympathetic projections innervated specific sites in the feline stomach.
Gastroenterology
95:
277-288,
1988[ISI][Medline].
23.
Page, AJ,
and
Blackshaw LA.
GABAB receptors inhibit mechanosensitivity of primary afferent endings.
J Neurosci
19:
8597-8602,
1999
24.
Pedarzani, P,
Kulik A,
Muller M,
Ballanyi K,
and
Stocker M.
Molecular determinants of Ca2+-dependent K+ channel function in rat dorsal vagal neurones.
J Physiol (Lond)
527:
283-290,
2000
25.
Powley, TL,
Berthoud HR,
Fox EA,
and
Laughton W.
The dorsal vagal complex forms a sensory-motor lattice: the circuitry of gastrointestinal reflexes.
In: Neuroanatomy and Physiology of Abdominal Vagal Afferents, edited by Ritter S,
Ritter RC,
and Barnes CD.. Boca Raton, FL: CRC, 1992, p. 55-79.
26.
Rinaman, L,
Card JP,
Schwaber JS,
and
Miselis RR.
Ultrastructural demonstration of a gastric monosynaptic vagal circuit in the nucleus of the solitary tract in rat.
J Neurosci
9:
1985-1996,
1989[Abstract].
27.
Rusin, KI,
and
Moises HC.
µ-Opioid and GABAB receptors modulate different types of Ca2+ currents in rat nodose ganglion neurons.
Neuroscience
85:
939-956,
1998[ISI][Medline].
28.
Sah, P.
Different calcium channels are coupled to potassium channels with distinct physiological roles in vagal neurons.
Proc R Soc Lond B Biol Sci
260:
105-111,
1995[ISI][Medline].
29.
Sah, P,
and
McLachlan EM.
Potassium currents contributing to action potential repolarization and the afterhyperpolarization in rat vagal motoneurons.
J Neurophysiol
68:
1834-1841,
1992
30.
Shapiro, RE,
and
Miselis RR.
The central organization of the vagus nerve innervating the stomach of the rat.
J Comp Neurol
238:
473-488,
1985[ISI][Medline].
31.
Sivarao, DV,
Krowicki ZK,
and
Hornby PJ.
Role of GABAA receptors in rat hindbrain nuclei controlling gastric motor function.
Neurogastroenterol Motil
10:
305-313,
1998[ISI][Medline].
32.
Travagli, RA,
Gillis RA,
Rossiter CD,
and
Vicini S.
Glutamate and GABA-mediated synaptic currents in neurons of the rat dorsal motor nucleus of the vagus.
Am J Physiol Gastrointest Liver Physiol
260:
G531-G536,
1991
33.
Travagli, RA,
Lewis MW,
and
Browning KN.
Effects of baclofen on identified rat dorsal motor nucleus of the vagus (DMV) neurons projecting to the stomach or intestine (Abstract).
Soc Neurosci Abstr
29 (380):
3,
1999.
34.
Travagli, RA,
Ulivi M,
and
Wojcik WJ.
Gamma-aminobutyric acid-B receptors inhibit glutamate release from cerebellar granule cells: consequences of inhibiting cyclic AMP and calcium influx.
J Pharmacol Exp Ther
258:
903-909,
1991[Abstract].
35.
Wojcik, WJ,
Travagli RA,
Costa E,
and
Bertolino M.
Baclofen inhibits with high affinity an L-type-like voltage-dependent calcium channel in cerebellar granule cell cultures.
Neuropharmacology
29:
969-972,
1990[ISI][Medline].