Strychnine Research Articles

Gycine and GABA interact to regulate the nitric oxide/cGMP signaling pathway in the turtle retina

Nitric oxide (NO) is a free radical that is important in retinal signal transduction and cyclic guanosine monophosphate (cGMP) is a critical downstream messenger of NO. The NO/cGMP signaling pathway has been shown to modulate neurotransmitter release and gap junction coupling in horizontal cells and amacrine cells, and increase the gain of the light response in photoreceptors. However, many of the mechanisms controlling the production of NO and cGMP remain unclear. Previous studies have shown activation of NO/cGMP production in response to stimulation with N-methyl-d-aspartate (NMDA) or nicotine, and the differential modulation of cGMP production by GABA(A) and GABA(C) receptors (GABA(A)Rs and GABA(C)Rs). This study used cGMP immunocytochemistry and NO imaging to investigate how the inhibitory GABAergic and glycinergic systems modulate the production of NO and cGMP. Our data show that blocking glycine receptors (GLYR) with strychnine (STRY) produced moderate increases in cGMP-like immunoreactivity (cGMP-LI) in select types of amacrine and bipolar cells, and strong increases in NO-induced fluorescence (NO-IF). TPMPA, a selective GABACR antagonist, greatly reduced the increases in cGMP-LI stimulated by STRY, but did not influence the increase in NO-IF stimulated by STRY. Bicuculline (BIC), a GABA(A)R antagonist, however, enhanced the increases in both the cGMP-LI and NO-IF stimulated by STRY. CNQX, a selective antagonist for alpha-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid hydrobromide/kainic acid (AMPA/KA) receptors, eliminated both the increases in cGMP-LI and NO-IF stimulated by STRY, while MK801, a selective antagonist for NMDA receptors, slightly increased the cGMP-LI and slightly decreased the NO-IF stimulated by STRY. Finally, double labeling of NO-stimulated cGMP and either GLY or GABA indicated that cGMP predominantly colocalized with GLY. Taken together, these findings support the hypothesis that GLY and GABA interact in the regulation of the NO/cGMP signaling pathway, where GLY primarily inhibits NO production and GABA has a greater effect on cGMP production. Such interacting inhibitory pathways could shape the course of signal transduction of the NO/cGMP pathway under different physiological situations.

GABA-induced response in spiral ganglion cells acutely isolated from guinea pig cochlea

The physiological and pharmacological properties of γ-aminobutyric acid (GABA)-induced responses were investigated in acutely isolated spiral ganglion cells (SGCs) of guinea pig by using either a nystatin-perforated patch recording configuration or a conventional whole-cell patch recording mode combined with rapid drug application. GABA and GABA A subtype receptor agonist, muscimol, induced inward currents in a concentration-dependent manner in 74% of all cells. The current-voltage relationship for the GABA response indicated the GABA-induced current in SGCs is carried by Cl −. Bicuculline (BIC), strychnine (STR), and picrotoxin (PTX) suppressed the GABA response in a concentration-dependent manner. BIC and STR, and PTX blocked the GABA response in a competitive manner and in a non-competitive manner, respectively. For inorganic antagonists, Cd 2+ and Ni 2+ also inhibited the GABA response. On the other hand, Zn 2+ failed to suppress the GABA response in SGCs. An antibiotic, benzylpenicillin, suppressed the GABA response. The GABA response was augmented by both a barbiturate derivative, pentobarbital (PB), and a benzodiazepine derivative, diazepam. The results suggest clearly that the physiological and pharmacological characteristics of GABA A receptor on acutely isolated guinea pig SGCs are quite similar to the common GABA A receptor found in other sensory ganglion cells.

Strychnine and brucine self-assemblies: structures and properties

Strychnine and brucine self-assemblies: structures and properties

Combined antagonism of aminergic excitatory and amino acid inhibitory receptors in the XII nucleus abolishes REM sleep-like depression of hypoglossal motoneuronal activity.

It is hypothesized that the suppression of motor activity (atonia) that occurs during REM sleep is caused by the combined inhibition of motoneurons by glycine or GABA and withdrawal of excitation mediated by serotonin and norepinephrine. However, it is not known whether these mechanisms can fully account for the atonia. In urethane-anesthetized, paralyzed and artificially ventilated rats, REM sleep-like episodes can be repeatedly elicited by microinjections of a cholinergic agonist, carbachol, into the dorsomedial pons. We used this model to determine whether microinjections of a combination of antagonists of serotonergic, adrenergic, GABA(A) and glycinergic receptors (methysergide, prazosin, bicuculline and strychnine) into the XII nucleus can abolish the carbachol-induced depression of XII motoneuronal activity. REM sleep-like episodes were elicited prior to, and at different times after, antagonist microinjections. In all six rats studied, the depression of XII motoneuronal activity did not occur when tested 30-60 min after the antagonists, whereas other characteristic features of the response (latency, duration, the appearance of hippocampal theta rhythm, activation of the cortical EEG, slowing of the respiratory rate) remained intact. The carbachol-induced depression partially recovered after 2-3 hours. We conclude that the REM sleep-like depression of XII motoneuronal activity can be fully accounted for by all or some of the following mechanisms: a withdrawal of motoneuronal excitation mediated by norepinephrine and serotonin and increased inhibition mediated by GABA and glycine.

Anxiolytic and anticonvulsive activity of Sesbania grandiflora leaves in experimental animals.

Various parts of Sesbania grandiflora have been used in the Indian system of medicine, in particular, the leaves of S. grandiflora are used in Ayurveda for the treatment of epileptic fits. In the present study we have evaluated the anticonvulsive activity of S. grandiflora leaves using a variety of animal models of convulsions. Bioassay guided separation was also carried out to identify the fraction possessing anticonvulsant activity. The benzene:ethyl acetate fraction (BE) of the acetone soluble part of a petroleum ether extract significantly delayed the onset of convulsions in pentylenetetrazol (PTZ) and strychnine (STR)- induced seizures in mice and reduced the duration of tonic hindleg extension in the maximum electroconvulsive shock (MES) induced seizures in mice. The BE contained a triterpene as a major component. In addition, the BE also inhibited electrically induced kindled seizures in mice and lithium-pilocarpine-induced status epilepticus in rats. It prolonged the duration of sleep induced by pentobarbital and antagonized the effect of D-amphetamine. Mice treated with BE preferred to remain in the open arm of the elevated plus maze indicating anxiolytic activity. The BE raised the brain contents of gamma-aminobutyric acid and serotonin. Thus the triterpene containing fraction of S. grandiflora exhibits a wide spectrum of anticonvulsant profile and anxiolytic activity.

Serotonin potentiation of glycine-activated whole-cell currents in the superficial laminae neurons of the rat spinal dorsal horn is mediated by protein kinase C

The modulatory effects of serotonin (5-HT) on glycine (Gly)-activated whole-cell currents were investigated in neurons acutely dissociated from the superficial laminae (I and II) of the rat spinal dorsal horn using the nystatin-perforated patch recording configuration under voltage-clamp conditions. Our results demonstrate that (1) Gly acted on strychnine (STR)-sensitive Gly receptors and elicited inward Cl − currents ( I Gly) at a holding potential of −40 mV; (2) 5-HT potentiated I Gly without affecting the reversal potential of I Gly; (3) the agonist ( α-methyl-5-HT) and antagonist (ketanserine) of 5-HT 2 receptor mimicked and blocked the potentiating effect of 5-HT on I Gly, respectively; (4) bisindolylmaleimide I (BIM), a selective inhibitor of protein kinase C (PKC), reduced the potentiating effect of 5-HT on I Gly; and (5) 5-HT-induced enhancement of I Gly was not affected by pretreatment with 1,2-bis-(2-aminophenoxy) ethane- N, N, N′, N′-tetraacetic acid tetrakis (acetoxy-methyl) ester (BAPTA AM), a Ca 2+ chelator. These results indicate that (1) the potentiation of 5-HT on I Gly is mediated by 5-HT 2 receptor and through Ca 2+-independent PKC intracellular signal transduction pathway; and (2) the interactions between 5-HT and Gly might modulate the transmission of nociceptive information through the spinal cord.

State-Related Inhibition by GABA and Glycine of Transmission in Clarke's Column

During the state of active sleep (AS), Clarke9s column dorsal spinocerebellar tract (DSCT) neurons undergo a marked reduction in their spontaneous and excitatory amino acid (EAA)-evoked responses. The present study was performed to examine the magnitude, consistency of AS-specific suppression, and potential role of classical inhibitory amino acids GABA and glycine (GLY) in mediating this phenomenon. AS-specific suppression of DSCT neurons, expressed as the reduction in mean spontaneous firing rate during AS versus the preceding episode of wakefulness, was compared across three consecutive sleep cycles (SC), each consisting of wakefulness (W), AS, and awakening from AS (RW). Spontaneous spike rate did not differ during W or RW between SC1, SC2, and SC3. AS-specific suppression of spontaneous firing rate was found to be consistent and measured 40.3, 31.5, and 41.6% in SC1, SC2, and SC3, respectively, indicating that such inhibition is marked and stable for pharmacological analyses. Microiontophoretic experiments were performed in which the magnitude of AS-specific suppression of spontaneous spike activity was measured over three consecutive SCs: SC1-control (no drug), SC2-test (drug), and SC3-recovery (no drug). The magnitude of AS-specific suppression during SC2-test measured only 11.7 or 14.6% in the presence of GABA_A antagonist bicuculline (BIC) or GLY antagonist strychnine (STY), respectively. Coadministration of BIC and STY abolished AS-specific suppression. AS-specific suppression of EAA-evoked DSCT spike activity was also abolished in SC2-test after BIC or STY, respectively. We conclude that GABA and GLY mediate behavioral state-specific inhibition of ascending sensory transmission via Clarke9s column DSCT neurons.

Developmental lead exposure differentially alters the susceptibility to chemoconvulsants in rats

Sprague–Dawley rats were exposed to lead (Pb) acetate (0.2% w/v) in drinking water from postnatal day (PN) 1 through PN 25 followed by discontinuing Pb exposure for 25 days. The convulsion signs produced by the i.v. infusion of convulsants were observed at PN 25 and PN 50. Pb exposure significantly decreased pentylenetetrazol (PTZ)-, picrotoxin (PIC)-, and strychnine (STRY)-induced, but increased N-methyl- d-aspartate (NMDA) and 4-aminopyridine (4-AP)-induced convulsion thresholds at PN 25. After rehabilitation, the Pb-induced changes in PTZ-, NMDA- and 4-AP- induced convulsions persisted till PN 50. In contrast, the thresholds for PIC- and STRY-induced convulsions were reversed to an increase at PN 50. Blood Pb concentrations were 46.9±6.8 and 11.4±1.1 μg/dl at PN 25 and PN 50, respectively. The results demonstrate that developmental Pb exposure does not result in a global and persistent lowering of threshold in response to convulsive stimuli and the Pb-induced changes may be due to a selective modulation of inhibitory and excitatory neurotransmission depending on age and Pb concentration in blood.

Das schreckhafte M�dchen

Hintergrund. Hauptmerkmale der hereditaren Hyperekplexie sind in der fruhen Sauglingszeit eine flexorenbetonte Muskelhypertonie, im spateren Kindes- und Jugendalter eine ubersteigerte Reaktion auf Schreckreize mit Hinsturzen unter Verlust der Schutzreflexe. Ursache ist eine durch Mutationen auf Chromosom 5q bedingte Dysfunktion des strychninsensitiven Glyzinrezeptors. Fallbericht. Ein 15-jahriges Madchen wurde wegen Commotio cerebri auf unsere Kinderstation aufgenommen. Anamnestisch bestanden eine massive neonatale Muskelhypertonie, bilaterale Inguinalhernien, ubersteigerte Schreckreaktionen mit Apnoen in der Sauglingszeit und Sturzen im spateren Kindesalter. Die Diagnose Hyperekplexie wurde gestellt. Unter Clobazam traten wahrend der bisher einjahrigen Nachbeobachtungszeit keine schreckassoziierten Sturze mehr auf. Diskussion. Eine adaquate Therapie der auch unter Padiatern nur wenig bekannten Hyperekplexie ist fur die Prognose entscheidend.

Woodward, Robinson, and Strychnine: Chemical Structure and Chemists' Challenge

L'A. demontre comment la structure chimique de la strychnine a ete etablie malgre l'opposition entre deux celebres chimistes du XX e siecle, Woodward (R.) et Robinson (R.)

BN52021, a platelet activating factor antagonist, is a selective blocker of glycine-gated chloride channel

We have found that the platelet activating factor antagonist (BN52021) is an effective blocker of the glycine (Gly) receptor-mediated responses in the hippocampal pyramidal neurons of rat. Using the whole-cell voltage clamp and concentration clamp recording techniques, we investigated the mechanism underlying the inhibitory action of this terpenoid on the glycine-induced chloride current. BN52021 selectively and reversibly inhibits glycine current in a non-competitive and voltage-dependent fashion. The antagonistic effect of this substance is more pronounced at positive membrane potentials. At holding potential −70 mV and in the presence of 200 μM glycine IC 50 value for the blocking action of BN52021 was 270±10 nM. Repetitive applications of BN52021 reveal the use-dependence of its blocking action. When co-applied with strychnine (STR), a competitive glycine receptor antagonist, BN52021 does not alter the IC 50 value for strychnine. The inhibitory effect of BN52021 on gamma-aminobutyric acid (GABA) current is at least 25 times less potent than the effect on glycine current. This substance fails to affect AMPA and NMDA responses. It may be concluded that BN52021 inhibits glycine-gated Cl − channels by interacting with the pore region and does not compete for the strychnine-binding centre.

Anticonvulsant activities of the FS-1 subfraction isolated from roots of Delphinium denudatum.

Delphinium denudatum Wall. (Ranunculaceae) is a medicinal herb used for the treatment of epilepsy in the subcontinent. The present study reports the anticonvulsant activities in the maximal electroshock test (MEST) and subcutaneous pentylenetetrazole (PTZ), bicuculline (BIC), picrotoxin (PIC)-induced seizures of the FS-1 subfraction (FS-1) that was obtained by purification of an aqueous fraction isolated from the roots of D. denudatum. In CF 1 mice, FS-1 (600 mg/kg i.p.) exhibited very potent anticonvulsant activity that was comparable to the effects of the well-known antiepileptic drug phenytoin (20 mg/kg) in MEST and protected 100% animals from hind limb tonic extension phase of this model. FS-1 also suppressed PTZ-induced threshold seizure and the loss of the righting reflex with tonic fore and hind limb extension by 100%, similar to the antiepileptic drug valproic acid (350 mg/kg). BIC-induced seizures were suppressed in 80% of the animals. FS-1 exhibited weak anticonvulsant effect on PIC-induced seizures, however, it significantly reduced mortality and delayed the onset of seizures. FS-1 had no effect on strychnine (STN)-induced extensor seizures. The results demonstrate the broad and potent anticonvulsant activity of the compounds in FS-1 of D. denudatum.

Acute exposure to trichloroethylene differentially alters the susceptibility to chemoconvulsants in mice

The effects of a common industrial solvent, trichloroethylene (TCE), which was once used as an anesthetic agent but its in vivo mechanism is still unknown, on convulsant-induced seizures in mice were examined. Pretreatment with TCE (250–2000 mg/kg, i.p.) significantly increased pentylenetetrazol (PTZ)-, picrotoxin (PIC)-, bicuculline (BIC)-, strychnine (STY)-, 4-aminopyridine (4-AP)- and N-methyl- d-aspartate (NMDA)-induced convulsion thresholds and lethal doses. However, the increase in convulsion thresholds and lethal doses was much greater for GABAergic antagonists (PIC, BIC, and PTZ) than non-GABAergic convulsants (STY, 4AP, and NMDA) following 2000 mg/kg TCE administration. Pre-treatment of mice with disulfiram (an inhibitor of CYP 4502E1) but not 4-methyl pyrazole (an inhibitor of alcohol dehydrogenase) significantly prolonged the time required for TCE (5000 mg/kg, i.p.) to induce the loss of righting reflex. These results suggest that acute exposure to TCE differentially alters the susceptibility to chemically induced convulsions in mice. The anticonvulsive effect of TCE may be predominantly mediated by GABA A receptors. In addition, TCE appears to exert a direct anesthetic effect.

The mouse sperm glycine receptor/chloride channel: cellular localization and involvement in the acrosome reaction initiated by glycine.

Previously, we reported that glycine initiates the in vitro acrosome reaction (AR) of porcine and human sperm by a mechanism that includes the glycine receptor/Cl- channel (GlyR) and that this receptor/channel is required for the zona-pellucida-initiated AR. Because mouse sperm are important tools in the study of fertilization, we investigated whether glycine initiated the mouse sperm AR and whether the sperm GlyR was involved in that initiation. Glycine (250 microM to 1 mM) initiated the AR of capacitated but not noncapacitated mouse sperm. The glycine-initiated AR was significantly inhibited by 50 nM strychnine, a neuronal GlyR antagonist. The neuronal GlyR agonists taurine and beta-alanine did not initiate the AR at 1 mM or 5 mM. A monoclonal antibody against the rat spinal cord GlyR significantly inhibited the glycine-initiated AR but not the spontaneous AR. Indirect immunofluorescence localization studies with that monoclonal antibody and postfixed live sperm detected 3 patterns of immunoreactivity involving 2 sites in the periacrosomal plasma membrane. These patterns were as follows: type A localization on the plasma membrane overlying the tip of the anterior acrosomal region; type B localization on the plasma membrane overlying the posterior part of the acrosomal equatorial segment and/or, in acrosome-reacted sperm, the posterior part of the modified equatorial segment; and type C localization that included both type A and type B. Type A and type C localization were only observed on the acrosome-intact sperm. During capacitation, the number of the sperm showing type A localization increased. Our results demonstrate that mouse sperm provide an excellent model for studying the role of the GlyR in the acrosome reaction.

Naming and toxicity: A history of strychnine

Naming and toxicity: A history of strychnine

γ-Aminobutyric acid-induced responses in acutely dissociated neurons from the rat sacral dorsal commissural nucleus

The electrophysiological and pharmacological properties of GABA-activated Cl − currents ( I GABA) were investigated in enzymatically dissociated rat sacral dorsal commissural nucleus (SDCN) neurons using the nystatin perforated patch recording configuration under voltage-clamp conditions. Exogenous application of GABA to SDCN neurons induced Cl − currents which increased in a concentration-dependent manner. Bicuculline (BIC) and strychnine (STR) antagonized the I GABA in a concentration-dependent manner. Zn 2+ suppressed the I GABA with an IC 50 of 2.8×10 −5 M. Muscimol mimicked the I GABA, while baclofen evoked no response. Pentobarbital (PB) and 5β-pregnan-3α-ol-20-one (pregnanolone, PGN) also induced GABA A-mimic Cl − currents. Diazepam (DZP), PB and PGN all enhanced the I GABA by increasing the apparent affinity of the GABA A receptors to GABA. Moreover, spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) were observed in mechanically dissociated SDCN neurons attached with synaptic boutons, so called `synaptic bouton preparation'. These results indicate that SDCN neurons express GABA A receptors with relatively low sensitivity to Zn 2+ inhibition, and that GABA may have a functional role as an inhibitory transmitter in the SDCN regulating nociceptive, analgesic, and autonomic functions.

Milacemide, a glycine pro-drug, inhibits strychnine-allodynia without affecting normal nociception in the rat

The blockade of spinal glycine receptors with intrathecal (i.t.) strychnine (STR) produces reversible, segmentally localized allodynia in the rat. The purpose of this study was: (1) to investigate the effect of the anticonvulsant agent, milacemide, a glycine pro-drug on STR-allodynia; (2) to compare this effect with that of milacemide on normal nociception (without STR); and (3) to determine the sensitivity of the anti-allodynic effect of milacemide to pretreatment with selective monoamine oxidase (MAO)-A (clorgyline) and MAO-B ( l-deprenyl) inhibitors. Male Sprague–Dawley rats, fitted with chronic i.t. catheters, were lightly anesthetized with urethane. Hair deflection (HD) evoked maximum changes in blood pressure and heart rate were recorded from left carotid artery, and cortical electroencephalographic (EEG) activity was continuously monitored using subdermal needle electrodes before and after i.t. STR (40 μg). Rats were pretreated with a single intravenous (i.v.) injection of milacemide (100–600 mg/kg), 1 h before i.t. STR. To sustain the allodynic state, STR was injected every hour for up to 4 h. HD was applied to the affected dermatomes (2 min duration) using a cotton-tipped applicator at 5-min intervals for the duration of the STR effect. Normally innocuous HD elicited a marked increase in mean arterial blood pressure and heart rate, an immediate motor responses, and desynchronisation of EEG when applied to the cutaneous dermatomes affected by i.t. STR. Milacemide (100–600 mg/kg, i.v.) dose-dependently inhibited the heart rate and pressor responses (ED 50=398 mg/kg; 95%CI=196–873) and the motor responses (ED 50=404 mg/kg; 95%=CI 275–727). Maximum inhibition was observed approximately 2 h after i.v. injection. The duration of action ranged from 3 h (400 mg/kg) to 4 h (600 mg/kg). Milacemide had no effect on the percent synchrony in the EEG. At the time of maximum inhibition of STR-allodynia (2 h post-infusion), responses evoked by noxious pinch were unaffected by milacemide. Pretreatment with l-deprenyl (3 mg/kg, i.p.), but not clorgyline (10 mg/kg, i.p.) significantly blocked the anti-allodynic effect of milacemide (600 mg/kg i.v). These data indicate that i.v. milacemide significantly attenuates the allodynia arising from spinal glycine receptor blockade, and are consistent with: (1) the selective modulation of low threshold afferent input by STR-sensitive, glycine interneurons in the rat spinal cord; and (2) the pharmacological actions of milacemide as a glycine pro-drug.

A Developmental Shift from GABAergic to Glycinergic Transmission in the Central Auditory System

GABAergic and glycinergic circuits are found throughout the auditory brainstem, and it is generally assumed that transmitter phenotype is established early in development. The present study documents a profound transition from GABAergic to glycinergic transmission in the gerbil lateral superior olive (LSO) during the first 2 postnatal weeks. Whole-cell voltage-clamp recordings were obtained from LSO neurons in a brain slice preparation, and IPSCs were evoked by electrical stimulation of the medial nucleus of the trapezoid body (MNTB), a known glycinergic projection in adult animals. GABAergic and glycinergic components were identified by blocking transmission with bicuculline and strychnine (SN), respectively. In the medial limb of LSO, there was a dramatic change in the GABAergic IPSC component, decreasing from 78% at postnatal day 3 (P3)-P5 to 12% at P12-P16. There was an equal and opposite increase in the glycinergic component during this same period. Direct application of GABA also elicited significantly larger amplitude and longer duration responses in P3-P5 neurons compared with glycine-evoked responses. In contrast, MNTB-evoked IPSCs in lateral limb neurons were more sensitive to SN throughout development. Consistent with the electrophysiological observations, there was a reduction in staining for the beta2,3-GABAA receptor subunit from P4 to P14, whereas staining for the glycine receptor-associated protein gephyrin increased. Brief exposure to baclofen depressed transmission at excitatory and inhibitory synapses for approximately 15 min, suggesting a GABAB-mediated metabotropic signal. Collectively, these data demonstrate a striking switch from GABAergic to glycinergic transmission during postnatal development. Although GABA and glycine elicit similar postsynaptic ionotropic responses, our results raise the possibility that GABAergic transmission in neonates may play a developmental role distinct from that of glycine.

Glycine-activated chloride currents of neurons freshly isolated from the ventral tegmental area of rats

Properties of whole-cell glycine currents ( I Gly) of ventral tegmental area (VTA) neurons from 3- to 7-day old Sprague–Dawley rats were investigated with the patch-clamp technique. Ninety-three percent of the 126 neurons examined produced I Gly in response to glycine. For 70% of these neurons, I Gly did not decay in response to a threshold concentration of glycine (1–5 μM). At elevated glycine concentrations, I Gly consistently decayed from a peak to a steady state (SS). I Gly increased in amplitude sigmoidally as a function of the concentration of agonist with an EC 50 of 32 μM. Strychnine (STR), when co-applied with glycine after a prepulse of STR, suppressed both the peak and SS I Gly noncompetitively. In the absence of a prepulse, STR had a smaller effect on peak I Gly while increasing its decay rate; the SS amplitude decreased. These STR effects were concentration dependent with an IC 50 of 31 nM and 184 nM STR for the peak and SS I Gly, with prepulse, respectively, and 732 nM and 193 nM for the peak and SS I Gly, respectively, without prepulse. Picrotoxin (PTX) co-applied with glycine suppressed both the peak and the SS I Gly with an IC 50 of 25 μM. In contrast to STR, 1 min preincubation with PTX had no effect on I Gly. Thus, PTX acts on the open channel. The inhibitory effects of both STR and PTX on I Gly did not depend on the membrane potential.

Taurine-activated chloride currents in the rat sacral dorsal commissural neurons

The electrophysiological and pharmacological properties of taurine (Tau)-activated Cl − currents ( I Tau) were investigated in the dissociated rat sacral dorsal commissural nucleus (SDCN) neurons using the nystatin perforated patch recording configuration under voltage-clamp conditions. The reversal potential of I Tau was close to the Cl − equilibrium potential. The I Tau was not affected by a preceding GABA response but cross-desensitized by a preceding glycine (Gly) response. Strychnine (STR), picrotoxin (PIC), bicuculline (BIC) and Zn 2+ suppressed the I Tau in a concentration-dependent manner. The pharmacology of the I Tau and Gly-induced response ( I Gly) was similar, though Zn 2+ inhibition on I Tau differed from that on I Gly in being much slower in recovery. Serotonin potentiated the I Tau via protein kinase C. The results indicate that both Tau and Gly act on a strychnine-sensitive site to open the same Cl − channels in the SDCN neurons, and suggest that Tau may act as a functional neurotransmitter in the mammalian SDCN.