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The Journal of Neuroscience, October 18, 2006, 26(42):10717-10726; doi:10.1523/JNEUROSCI.3364-06.2006
Previous Article | Next Article
Cellular/Molecular
Identified Motoneurons Involved in Sexual and Eliminative Functions in the Rat Are Powerfully Excited by Vasopressin and Tachykinins
Roch Ogier, Eliane Tribollet, Philippe Suarez, andMario Raggenbass Department of Basic Neurosciences, University Medical Center, CH-1211 Geneva 4, Switzerland
Abstract
Top
Abstract
Introduction
The pudendal motor system is constituted by striated muscles of the pelvic floor and the spinal motoneurons that innervate them. It plays a role in eliminative functions of the bladder and intestine and in sexual function. Pudendal motoneurons are located in the ventral horn of the caudal lumbar spinal cord and send their axon into the pudendal nerve. In the rat, binding sites for vasopressin and tachykinin are present in the dorsomedial and dorsolateral pudendal nuclei, suggesting that these neuropeptides may affect pudendal motoneurons. The aim of the present study was to investigate possible effects of vasopressin and tachykinins on these motoneurons. Recordings were performed in spinal cord slices of young male rats using the whole-cell patch-clamp technique. Before recording, motoneurons were identified by 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4-chlorobenzenesulfonate retrograde labeling. The identification was confirmed, a posteriori, by choline acetyltransferase immunocytochemistry. Vasopressin and tachykinins caused a powerful excitation of pudendal motoneurons. The peptide-evoked depolarization, or the peptide-evoked inward current, persisted in the presence of tetrodotoxin, indicating that these effects were mainly postsynaptic. By using selective receptor agonists and antagonist, we determined that vasopressin acted via vasopressin 1a (V1a), but not V1b, V2, or oxytocin receptors, whereas tachykinins acted via neurokinin 1 (NK1), but not NK2 or NK3, receptors. Vasopressin acted by enhancing a nonselective cationic conductance; in some motoneurons, it also probably suppressed a resting K+ conductance. Our data show that vasopressin and tachykinins can excite pudendal motoneurons and thus influence the force of striated perineal muscles involved in eliminative and sexual functions.
Key words: cationic conductance; choline acetyltransferase; oxytocin; patch clamp; pudendal motoneurons; spinal cord
Introduction
Pudendal motoneurons are located in the ventral horn of the caudal lumbar spinal cord and project into the pudendal nerve. They innervate striated pelvic muscles involved in penile erection and ejaculation as well as the external urethral and anal sphincters. In most mammals, pudendal motoneurons are found within a single cell group, the Onuf's nucleus (Ueyama et al., 1984; Roppolo et al., 1985
The properties of pudendal motoneurons suggest that they constitute a neuronal population distinct from other motoneurons. (1) They are sexually dimorphic, a property shared by their target muscles (Breedlove and Arnold, 1980
Pudendal motoneurons play a critical role in sexual and eliminative functions, and lesions in pathways controlling their activity can be devastating. Knowledge of their sensitivity to neurotransmitters/neuromodulators may be important for rescuing at least part of these functions in case of spinal cord injury or disease. Although some information on the basic electrophysiological properties of cat and rat pudendal motoneurons is available (Manabe et al., 1991
Materials and Methods
Spinal cord slices. Rats used were of the Sprague Dawley strain (Charles River Laboratories, Iffa Credo, L'Arbresle, France). Neonate male animals, 6–10 d old, were anesthetized (pentobarbital, 50 mg/kg, i.p.) and killed by decapitation in accordance with the rules of the Swiss Federal Veterinary Office. The spinal cord was rapidly removed, and the lumbosacral region was isolated, embedded in 5% agar, and submerged in ice-cold perfusion solution (see below), saturated with 95% O2/5% CO2 and from which Ca2+ was omitted. Transverse slices, 300 µm thick, were cut using a vibrating microtome (Campden Instruments, Loughborough, UK). A slice containing pudendal motor nuclei was transferred to a recording chamber mounted on a Nikon (Tokyo, Japan) Eclipse E600FN, equipped with 40x, 0.8 numerical aperture water-immersion objective, differential interference contrast optics, and an infrared-sensitive video camera (C 25400-07; Hamamatsu, Schüpfen, Switzerland). Slices were continuously perfused with a solution containing the following (in mM): 135 NaCl, 15 NaHCO3, 5 KCl, 1 MgCl2, 2 CaCl2, and 10 glucose (saturated with 95% O2/5% CO2, pH 7.3–7.4, and thermoregulated at 32–33°C). Before whole-cell recordings, pudendal motoneurons labeled retrogradely with Fast DiI were visualized under fluorescence with the help of appropriate filters. All of the compounds tested were added to the perfusion solution at the concentration indicated.Whole-cell recordings. Whole-cell current-clamp and voltage-clamp recordings were performed using patch pipettes pulled from borosilicate glass capillaries (1.5 mm outer diameter and 0.86 mm internal diameter; Harvard Apparatus, Les Ulis, France). In most recordings, pipettes were filled with the following solution (in mM): 140 K-gluconate, 10 KCl, 10 HEPES, 4 MgCl2, 0.1 BAPTA, 2 Na2-ATP, 0.4 Na2-GTP, pH 7.2–7.3 adjusted with NaOH. Some recordings were done with a pipette solution in which K-gluconate and KCl were replaced by an equimolar amount of CsCl. For these pipette solutions, the calculated liquid junction potentials were 14.9 and 7.3 mV, respectively (Clampex Junction Potential Calculator; pClamp software). In view of histological identification of the recorded motoneuron, the pipette solution was sometimes supplemented with 5 mM biocytin. Current and voltage signals were recorded, amplified, and digitized using an Axopatch 200A amplifier, a Digidata 1320A interface, and pClamp software (Molecular Devices, Sunnyvale, CA). Current signals were low-pass filtered at 2 kHz and digitized at 5–10 kHz. Series resistance was compensated by 60–80%. Uncompensated series resistance >30 M
resulted in rejection of the recording. Average data are expressed as mean ± SEM.
Labeling of motoneurons. Intraperitoneal injection of fluorescent dyes, such as fast blue, true blue, or fluorogold, labels efficiently spinal cord motoneurons and autonomic neurons (Leong and Ling, 1990
Immunocytochemistry. To assess the anatomical organization of pudendal motor nuclei in neonate rats, male animals aged of 10–13 d were anesthetized as described above and perfused through the left ventricle by gravity feed with physiological saline for 2 min, followed by 50 ml of fixative solution, i.e., 4% paraformaldehyde in 0.1 M PBS, pH 7.4. The lumbosacral portion of the spinal cord was dissected out, postfixed overnight in the same fixative solution, immersed for 2 d in a 30% sucrose solution in PBS, and cut in 40-µm-thick coronal sections in a cryostat. Sections were collected in PBS and bathed 30 min in PBS containing 0.3% hydrogen peroxide, to suppress endogenous peroxidase activity, 30 min in PBS containing 0.5% caseine, and 30 min (three times for 10 min) in PBS containing 0.3% Triton X-100, 0.1 M L-lysine, and 0.1% sodium azide. Sections were then incubated overnight at room temperature under constant agitation with a goat polyclonal antibody to ChAT at 1:250 (AB144P; Chemicon, Temecula, CA). Immunostaining was performed using a biotinylated horse anti-goat antibody at 1:200 (BA-9500; Vector Laboratories, Burlingame, CA) and an avidin–biotin detection system (Vectastain Elite, ABC kit; Vector Laboratories) according to the protocol of the manufacturer. Both the primary and the secondary antibodies were diluted in PBS containing 0.3% Triton X-100, 0.1 M L-lysine, and 0.1% sodium azide. The sections were then rinsed twice (two times for 10 min) in PBS, rinsed once in distilled water, mounted onto gelatin–chrome alum-coated slides, dried, dehydrated with ethanol, and embedded in Eukitt. Sections were examined with bright-field illumination.
To confirm that the recorded neurons were motoneurons, spinal cord slices containing biocytin-filled cells were processed for ChAT immunocytochemistry. Slices were first immersed for 2 h in 4% paraformaldehyde dissolved in 0.1 M PBS, pH 7.4, and then overnight in 30% sucrose dissolved in the same buffer. They were frozen flat between two glass coverslips and cut into 40-µm-thick sections in a cryostat. Sections were mounted onto gelatin–chrome alum-coated slides, washed with Tris–saline buffer (0.5 M Tris and 0.25 M NaCl, pH 7.4) for 20 min, and incubated for 4 h at room temperature in the presence of fluorescein isothiocyanate (FITC)-conjugated streptavidin (016-090-084; Jackson ImmunoResearch, West Grove, PA) at 1:150. The sections containing biocytin-labeled cells were then incubated overnight in the presence of the goat polyclonal antibody to ChAT (AB144P; Chemicon) at 1:100. Sections were further incubated for 4 h in the cyanine 3 (Cy3)-conjugated donkey anti-goat antibody (705-165-147; Jackson ImmunoResearch) at 1:50. All antibodies were diluted in Tris–saline buffer, with two washes for 10 min in Tris–saline buffer being performed between two successive steps. Labeled neurons were visualized with appropriate filters. Sections were photographed with the Olympus Optical (Tokyo, Japan) DP10 digital camera. Images were slightly adjusted for brightness and contrast using Adobe Photoshop software and were assembled using Adobe Illustrator software (Adobe Systems, San Jose, CA).
Chemical compounds. [Arg8]-vasopressin, [Thr4,Gly7]-oxytocin (TGOT), a selective oxytocin receptor agonist (Lowbridge et al., 1977
-ala8)-neurokinin A(4–10) (
Results
Identification of motoneurons
The distribution of ChAT immunoreactivity in spinal segment L6 of a 10-d-old male rat is illustrated in Figure 1A. Motoneurons are strongly immunoreactive, and their location is similar to that described at the same segmental level in the adult male rat (McKenna and Nadelhaft, 1986
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Figure 1. Identification of pudendal motoneurons in neonate rats. A, Coronal section of the spinal cord from a 10-d-old rat showing the immunostaining of ChAT at segmental level L6. Pudendal motoneurons are grouped in DM and DL nuclei. The RDL, which projects to the hindleg, and the ventral nucleus (V), which projects to the pelvic diaphragm, are also detectable, as are isolated immunoreactive cells scattered in the medial and dorsal central gray. B, Photomicrograph illustrating the Fast DiI retrograde labeling of DM motoneurons. The spinal cord section is from a 10-d-old rat that had received an intraperitoneal injection of Fast DiI 24 h before. The animal was fixed by intracardiac perfusion of a solution containing 4% paraformaldehyde in 0.1 M PBS. Note, by comparing A and B, that Fast DiI-labeled DM nuclei are easily recognizable by their shape and position along the midline. C, D, Identification of a recorded biocytin-loaded DM motoneuron. C, Biocytin was visualized by treatment of the section with FITC-conjugated streptavidin. D, The biocytin-labeled motoneuron was immunoreactive for ChAT, detected with a Cy3-conjugated secondary antibody. Scale bars: A, 200 µm; B, D (for B–D), 100 µm.
In total, recordings were obtained from 43 DM and 21 DL motoneurons identified by Fast DiI labeling. To further confirm that they were motoneurons, 12 DM motoneurons were injected with biocytin during the recording session and processed for ChAT immunoreactivity (Fig. 1C,D). All twelve were positive for ChAT and located within a medial ChAT-positive cell pool, identified as the DM nucleus. For comparison, recordings were also obtained from 21 identified nonpudendal motoneurons located in either the RDL nucleus or lumbar motor nuclei positioned rostrally to pudendal motor nuclei.Effect of vasopressin on identified DM and DL pudendal motoneurons
When recorded with K-gluconate-containing patch pipettes, DM pudendal motoneurons had an average cell input resistance of 91 ± 19 MThe effect of vasopressin on DM motoneurons was tested on a sample of 19 cells. In current clamp, the neuropeptide (0.1–0.5 µM) caused a reversible excitation in all motoneurons tested. In some motoneurons, which were silent in control conditions, the depolarization generated by vasopressin was sufficient to elicit action potential firing, the peak firing frequency being 8 ± 1 Hz (range, 5–12 Hz; n = 7) (Figs. 2, 3). The vasopressin-evoked depolarization ranged from 7 to 15 mV and was on average 11 ± 1 mV (n = 5). The peptide-induced depolarization persisted in the presence of tetrodotoxin (TTX) (0.5 µM) and was, on average, 11 ± 3 mV (range, 4–17 mV; n = 5) (Fig. 3). This suggests that the vasopressin effect was mainly, if not completely, postsynaptic. In motoneurons recorded in the voltage-clamp mode (holding potential, –55 to –75 mV), vasopressin evoked a sustained inward current that ranged from 45 to 200 pA and had an average value of 124 ± 22 pA (n = 7) (Fig. 3).
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Figure 2. Effect of vasopressin and of selective agonists of V1b and V2 receptors on an identified DM pudendal motoneuron. Current-clamp records obtained in the presence of 0.1 µM vasopressin (AVP; top and bottom traces), 1 µM d[Cha4]AVP (second trace), and 1 µM dVDAVP (third trace). In this figure and in Figures 3, 4, and 6
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Figure 3. Effect of vasopressin and of a selective oxytocin receptor agonist on an identified DM pudendal motoneuron. Current-clamp records obtained in the presence of 0.5 and 0.1 µM vasopressin (AVP; top and third traces, respectively), in the presence of 0.5 µM vasopressin and 0.5 µM TTX (fourth trace), and in the presence of 0.5 µM TGOT (second trace). The inset in the top trace shows a detail of the membrane potential at the beginning of the vasopressin-evoked firing. Bottom trace, Voltage-clamp recording showing the inward current elicited by vasopressin at 0.5 µM, in the presence of TTX, in this same motoneuron. Note that, contrary to vasopressin, TGOT, an oxytocin receptor agonist, did not induce any depolarization, although in this motoneuron it caused a slight increase in membrane noise. Note also that the vasopressin-induced depolarization and inward current persisted in the presence of TTX, i.e., in conditions of synaptic uncoupling.
The pharmacological profile of the receptors mediating the direct effect of vasopressin on pudendal motoneurons was determined by making use of selective agonists of vasopressin and oxytocin receptors. In DM pudendal motoneurons, the selective V2 receptor agonist dVDAVP (1 µM; n = 4) and the selective V1b receptor agonist d[Cha4]AVP (1 µM; n = 4) were without effect (Fig. 2). The oxytocin receptor agonist TGOT (0.1–0.5 µM) was tested on five motoneurons (three recorded in the normal perfusion solution, the remaining two in the presence of TTX at 0.5 µM). TGOT did not induce any depolarization in any of these motoneurons but slightly increased the membrane noise in some of them (Fig. 3, second trace). In contrast, in all of these cells, vasopressin (0.1–0.5 µM) evoked a depolarization or action potential firing.DL pudendal motoneurons had a cell input resistance of 76 ± 20 M
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Figure 4. Effect of vasopressin and of a V1a receptor antagonist on identified DL pudendal motoneurons. A, Current-clamp records obtained in the presence of 0.5 µM vasopressin (AVP; top trace) and in the presence of both vasopressin and 0.1 µM of the V1a selective antagonist VPA (bottom trace). B, Voltage-clamp records obtained in a second DL pudendal motoneuron. They show the inward current evoked by vasopressin at 0.5 µM (AVP; top trace) and by vasopressin coapplied with 50 nM of the V1a receptor antagonist VPA (bottom trace). Note that the V1a receptor antagonist suppressed the vasopressin response.
Together, our data show that pudendal motoneurons, located in either the DM or the DL nucleus, are directly excited by vasopressin acting on V1a receptors.Mechanism of action of vasopressin
To gain some information on the membrane mechanism responsible for the excitatory effect of vasopressin in pudendal motoneurons, we tested the effect of Cs+, a broad-spectrum blocker of K+ channels. Seven DM pudendal motoneurons were recorded using patch pipettes filled with a Cs-methanesulfonate-containing solution. In these motoneurons, vasopressin either elicited a depolarization of 7 ± 2 mV (range, 6–10 mV; n = 3) or generated an inward current of 98 ± 32 pA (range, 50–190 pA; n = 4). These results indicate that Cs-sensitive K+ channels probably do not play an exclusive role in the mechanism of action of vasopressin.In a second set of experiments, we tested the effect of vasopressin on the motoneuron current-voltage (I–V) relationship. I–V relationships were established in the absence (control I–V) and in the presence (test I–V) of vasopressin, added to the perfusion solution at 0.2–1 µM. The following protocol was used: the motoneuron was held at a depolarized potential for 0.75 s, a hyperpolarizing voltage ramp command was then delivered (rate 230 mV/s), and the current response was recorded. The net vasopressin-induced current was computed by subtracting the control I–V relationship from the test I–V relationship. In two motoneurons, recorded with K-gluconate-containing patch pipettes, the net vasopressin-evoked current showed slight outward rectification and reversed in polarity at –49 and –26 mV (Fig. 5A). In two other motoneurons, the vasopressin current was also slightly outward rectifying but failed to reverse at any potential. In three additional motoneurons, the vasopressin current varied linearly with the membrane potential and approached zero at hyperpolarized potentials, i.e., at –134, –120, and –114 mV (Fig. 5B). In one motoneuron, recorded with Cs-methanesulfonate-containing patch pipettes, the net vasopressin current reversed in polarity at –28 mV. These data suggest that, in some motoneurons, vasopressin acted by increasing a nonselective cationic conductance, whereas in other motoneurons, it acted via a dual mechanism, i.e., by increasing a cationic conductance and by concomitantly decreasing a resting K+ conductance.
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Figure 5. Current–voltage relationship of the vasopressin-activated current in identified DM pudendal motoneurons. A, B, Voltage-clamp commands were delivered as described in Results, in both the absence (control) and presence of 0.5 µM vasopressin (AVP). The net vasopressin-evoked current was obtained by subtraction. The motoneurons were recorded using K-gluconate-containing patch pipettes. The perfusion solution was supplemented with 0.5 µM TTX. Note that, in the motoneuron in A, the vasopressin-evoked current reversed in polarity at approximately –49 mV, whereas in the motoneuron in B, it approached zero at approximately –120 mV.
Effect of tachykinins on identified DM and DL pudendal motoneurons
The effect of tachykinins was tested on a sample of seven DM pudendal motoneurons in the current-clamp mode. All of the motoneurons responded to tachykinins. Substance P (0.1–1 µM) caused a depolarization in one motoneuron (5 mV) and elicited action potential firing in four motoneurons (peak firing frequency, 9 ± 1 Hz; range, 5–10 Hz) (Fig. 6A). In three motoneurons, recorded in the presence of TTX (0.5 µM), the substance P-evoked depolarization was 11 ± 1 mV (range, 10–12 mV), indicating that this compound acted postsynaptically.
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Figure 6. Effect of tachykinin receptor agonists on identified DM pudendal motoneurons. A, Current-clamp records obtained in the presence of 1 µM substance P (SP; top trace) and in the presence of 1 µM
The pharmacological profile of the receptor mediating the effect of tachykinins in DM motoneurons was determined by making use of selective agonists of tachykinin receptors. The selective NK1 receptor agonist sar9-SP (0.1–0.2 µM) mimicked the effect of substance P (n = 10). In four motoneurons, it induced a depolarization of 9 ± 1 mV (range, 7–10 mV), and, in two motoneurons, it elicited action potential firing (peak firing frequency, 7 and 11 Hz) (Fig. 6B). In four motoneurons recorded in the presence of TTX (0.5 µM), sar9-SP evoked a depolarization of 14 ± 3 mV (range, 5–19 mV) (Fig. 6C). The selective NK2 agonistIn the DL nucleus, substance P or sar9-SP excited all 10 tested motoneurons. Substance P (0.2–0.5 µM) caused a depolarization in two motoneurons (10 mV in both cases) and induced action potential firing in three motoneurons (peak firing frequency, 1, 3, and 4 Hz). sar9-SP (0.2–0.5 µM) elicited action potential firing (10 ± 2 Hz; range, 3–16 Hz; n = 5) (Fig. 7) or evoked, in the presence of TTX (0.25 µM), a depolarization of 17 ± 2 mV (range, 10–20 mV; n = 5) (Fig. 7).
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Figure 7. Effect of tachykinin receptor agonists on an identified DL pudendal motoneuron. Current-clamp records obtained in the presence of 0.5 µM sar9-SP (top trace), 0.5 µM
Together, our data indicate that pudendal motoneurons, located in either the DM or the DL nucleus, were directly excited by tachykinins acting on NK1 receptors.Effect of tachykinins on identified nonpudendal motoneurons
Recordings were performed in motoneurons innervating the hindleg, i.e., in six RDL motoneurons and in 15 lumbar motoneurons located rostrally to pudendal motoneurons. The data obtained in these two sets of motoneurons were similar and were pooled. They had a cell input resistance of 42 ± 15 M
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Figure 8. Effect of tachykinin receptor agonists on identified RDL and lumbar motoneurons. A, Current-clamp records obtained in an RDL motoneuron in the presence of 0.5 µM sar9-SP (top trace), 0.5 µM
In conclusion, nonpudendal motoneurons located in either the RDL nucleus or lumbar motor nuclei are directly excited by tachykinins acting on NK1 receptors.
Discussion
Pharmacology of vasopressin and tachykinin effects on pudendal motoneurons
The present data show that spinal motoneurons located in the DM and DL nuclei can be powerfully excited by vasopressin and tachykinins. Despite their anatomical segregation and functional specialization, DM and DL pudendal motoneurons appear to possess a similar sensitivity to these compounds.The action of vasopressin was attributable to activation of V1a but not V1b, V2, or oxytocin receptors. Our electrophysiological data are in good agreement with autoradiographic data showing the presence, in pudendal nuclei of male rats, of high-affinity vasopressin binding sites of the V1a type (Tribollet et al., 1997
We could not evidence any direct effect of TGOT, a selective oxytocin receptor agonist, on pudendal motoneurons. However, in some of them, TGOT caused an increase in membrane noise, probably attributable to enhanced synaptic input. A synaptically mediated inhibitory effect of vasopressin or oxytocin in lumbar motoneurons and in hypoglossal motoneurons has been characterized previously (Palouzier-Paulignan et al., 1994
The excitatory action of tachykinins on pudendal motoneurons was mediated exclusively by NK1 receptors. Although the pharmacological profile of substance P binding sites present in rat pudendal nuclei has not been characterized (Charlton and Helke, 1985
Comparison with nonpudendal motoneurons
Recently, we characterized the action of vasopressin on lumbar motoneurons, which innervate the hindleg and are located at spinal segments rostral to those containing pudendal motoneurons (Liu et al., 2003In the present study, we investigated the responsiveness to tachykinins of motoneurons innervating the hindleg and located in either the RDL nucleus or lumbar motor nuclei. These motoneurons were excited by either substance P or an NK1 receptor agonist. This effect was postsynaptic, because it persisted in the presence of TTX, i.e., in conditions of synaptic uncoupling. In contrast, NK2 and NK3 receptor agonists were ineffective in eliciting any direct response. It has been reported by others that tachykinins can induce depolarization or generate an inward current in nonpudendal spinal motoneurons or in brainstem motoneurons (Konishi and Otsuka, 1974
Together, our data indicate that pudendal motoneurons and motoneurons innervating the hindleg share a common sensitivity to vasopressin and tachykinins. Our study was performed in developing motoneurons, at a stage at which pudendal motoneurons do not yet express androgen receptors (Jordan et al., 1997
Mechanism of action of vasopressin
I–V relationships suggest that, in some pudendal motoneurons, vasopressin acted by enhancing a nonselective cationic conductance. In some other motoneurons, it probably exerted a dual effect: it enhanced a cationic conductance and, concomitantly, it suppressed a resting K+ conductance. We could not find any evidence that vasopressin could act solely by suppressing a K+ conductance. Indeed, (1) the vasopressin response persisted in motoneurons loaded with Cs, a nonspecific blocker of K+ channels; (2) in motoneurons in which the peptide-induced current was a linear function of membrane potential, zero current level was attained at potentials much more negative than the K+ equilibrium potential, EK, which, in our conditions, was –85 mV.A mechanism involving both a cationic conductance and K+ conductance has been proposed for the excitatory action of vasopressin in spinal lateral horn neurons and lumbar motoneurons of neonate rats (Kolaj and Renaud, 1998
In the present study, we did not address the membrane mechanism by which tachykinins excited pudendal motoneurons. Previous studies suggest that blockade of a K+ conductance may be involved. In neonatal lumbar motoneurons, the substance P-evoked depolarization was attributable to the suppression of a Ba+-sensitive K+ conductance (Fisher and Nistri, 1993
Possible origin of peptidergic innervation of pudendal motoneurons
Electrolytic lesion studies and retrograde tracing studies indicate that, in the rat and the cat, specific projections to pudendal motor nuclei originate from various brain areas, including the paraventricular hypothalamic nucleus (Holstege and Tan, 1987Functional considerations
In contrast to spinal motoneurons innervating the trunk and limb muscles and to brainstem motoneurons, virtually nothing is known about the pharmacological properties of pudendal motoneurons, and the present study is to our knowledge the first to address this issue. Our data indicate that vasopressin and tachykinins can regulate the activity of pudendal motoneurons. By modifying the intrinsic bioelectrical properties of motoneurons, vasopressin and tachykinins can modulate their input–output relationship (Hultborn and Kiehn, 1992
Footnotes
Received April 3, 2006; accepted Aug. 31, 2006.This work was supported in part by the Swiss National Science Foundation and the Fondation Carlos et Elsie de Reuter, Geneva, Switzerland (E.T., M.R.). R.O. was supported by the Swiss National Science Foundation MD–PhD program (Foundation Professor Max Cloëtta, Zurich, Switzerland). We thank Dr. M. Manning (Department of Biochemistry, Medical College of Ohio, Toledo, OH) for the supply of the V1b receptor agonist and the V1a receptor antagonist. We also thank D. Machard and A. Dupré for excellent technical assistance.
Correspondence should be addressed to Dr. Mario Raggenbass, Department of Basic Neurosciences, University Medical Center, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland. Email: mario.raggenbass{at}medecine.unige.ch
Copyright © 2006 Society for Neuroscience 0270-6474/06/2610717-10$15.00/0
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