Ionic mechanisms of the fast (nicotinic) phase of the acetylcholine response of identified Planorbarius corneus neurons

Responses to electrophoretic application of acetylcholine and suberyldicholine were investigated in identified neurons (LPed-2 and LPed-3) isolated from the left pedal ganglion ofPlanorbarius corneus. When microelectrodes filled with potassium chloride were used the reversal potentials of responses to acetylcholine and suberyldicholine were less negative than when microelectrodes filled with potassium sulfate were used; these reversal potentials were shifted toward depolarization if chloride ions in the medium were replaced by sulfate. These facts indicate that the responses in both LPed-2 and LPed-3 depend on chloride ions. Reversal potentials for acetylcholine and suberyldicholine in LPed-3 were virtually identical (–51 and –50 mV respectively), but in LPed-2 they differed significantly (–46 and –62 mV respectively). Replacement of sodium ions by Tris ions shifted the reversal potential for acetylcholine in LPed-2 toward hyperpolarization but did not change the reversal potential for suberyldicholine. Benzohexonium had the same action. The reversal potential for acetylcholine in medium with a reduced sodium concentration or in the presence of benzohexonium was the same as for suberyldicholine. It is concluded that on neuron LPed-2 acetylcholine activates both acetylcholine receptors which control conductance for chloride ions and acetylcholine receptors which change conductance for sodium ions, whereas suberyldicholine acts only on acetylcholine receptors responsible for the chloride conductance of the membrane.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 12, No. 5, pp. 533–540, September–October, 1980.     

The pharmacology of Limulus central neurons

1. Intracellular recordings have been made from neurons in the central nervous system of the horse-shoe crab, Limulus polyphemus. Neurons possess resting potentials between -40 and -60 mV, with action potentials ranging from 2-3 mV up to 60 mV in amplitude. Neurons also have excitatory and inhibitory postsynaptic potentials. 2. All the neurons studied are inhibited by GABA and excited by cholinomimetics. The GABA response is chloride mediated and reversibly antagonised by picrotoxinin but not by bicuculline or bicuculline methochloride or methoiodide. The cholinergic response is nicotinic and blocked by pentolinium, hexamethonium, chlorisondamine and dihydro-beta-erythroidine. 3. L-Glutamate can excite some cells, inhibit others and have a biphasic action, inhibition followed by excitation, on other cells. The inhibitory effect is chloride mediated and blocked by picrotoxinin. Ibotenate mimics the action of glutamate both in terms of inhibition and excitation but kainate and quisqualate only mimic the excitatory action of L-glutamate. 4. Dopamine, octopamine, 5-hydroxytryptamine and histamine excite some neurons while inhibiting others or have a biphasic action. Dopamine and octopamine normally have different effects on the same cell, suggesting they act via different receptors. Octopamine shows stereospecificity for the (-) isomer which is more than 100 times more active than the (+) isomer and octopamine is reversibly antagonised by phentolamine and cyproheptadine. 5. Proctolin has an excitatory action on these neurons and this effect is long lasting and can be potentiated by dibutyl cyclic AMP. 6. The pharmacology of Limulus central neurons is compared to the pharmacology of insect and crustacean central neurons. It is concluded that GABA and acetylcholine are central transmitters throughout the arthropods. It is also probable that L-glutamate and octopamine have a physiological role in the arthropod central nervous system. Proctolin appears to modify neuronal and muscle activity in the arthropods and has a modulatory or transmitter function.     

Uptake and stimulation-evoked release of tritiated neurotransmitters from slices of the rat rostral ventral medulla containing the nucleus raphe magnus: implications for pathways controlling nociception

1. The rostral ventral medulla plays a central role in the integration of nociceptive control. 2. Slices of this area of the brainstem may be labelled with tritiated noradrenaline, dopamine, serotonin, GABA and choline. 3. Uptake was greatest for noradrenaline and dopamine, GABA was intermediate and serotonin and choline were poorly accumulated. 4. Conditions for the release of all transmitter candidates except acetylcholine were established using either potassium or electrical stimulation and release was proven to be calcium dependent. 5. Electrophysiological and microinjection data are at variance with the commonly assumed actions of noradrenaline and dopamine and can be rationalized by the presence of a GABA interneuron integrating nociceptive input to the nucleus raphe magnus.     

Stimulus-dependent pacemaker activity in the distal canine lower esophageal sphincter

Electrical and mechanical properties of the distal canine lower esophageal sphincter were studied in vitro to investigate possible means of inducing pacemaker activity. Both direct excitation and block of potassium conductance were investigated. The acetylcholine analog, carbachol, induced tissue depolarization and increase in tone but no electrical slow waves. Tetraethylammonium (TEA) chloride induced depolarization and evoked continuous spiking activity and increase in tone. BaCl did not depolarize the tissue but low amplitude spiking activity developed and increased tone. The putative potassium channel blocker, aminacrine at 2 X 10(-4) M, induced electrical slow wave activity in the distal lower esophageal sphincter, with or without superimposed spikes, accompanied by phasic contractile activity. This activity closely resembled the spontaneous pacemaker activity observed previously in the proximal lower esophageal sphincter. The aminacrine-induced activity was abolished by calcium influx blockers. Aminacrine, but not TEA or BaCl, abolished the nonadrenergic nerve-mediated inhibitory junction potentials. In conclusion, block of inhibitory innervation, and induction of electrical slow waves as a control mechanism for phasic contractile activity, seems to require blockade of an aminacrine- but not TEA-sensitive potassium conductance.     

Ionic mechanisms of excitatory action of transmitter,exogenous acetylcholine,and serotonin on superior cervical ganglion neurons in rabbits

Ionic mechanisms of EPSP generation and depolarization induced by iontophoretic application of acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5-HT) — acetylcholine and serotonin potentials — were investigated in neurons of the isolated rabbit superior cervical ganglion by means of intracellular microelectrodes. The reversal potentials (E_r) for EPSP and the ACh-potential were –14.4±1.6 and –16.5±1.2 mV respectively, and they were about the same for the 5-HT potential. In some neurons (about one-third) much more negative values for E_r were obtained for EPSP and the ACh-potential by extrapolation, probably due to an increase in the resistance of their membrane during hyperpolarization. A decrease in the external sodium and potassium concentrations was shown to make E_r for EPSP and the ACh-potential more negative, whereas an increase in the external potassium concentration made it more positive than in normal solution; a change in the external chloride concentration did not alter E_r. It is suggested that the excitatory transmitter and exogenous ACh (and also, probably, 5-HT) share the same ionic mechanism of action of the membrane, which includes an increase in the permeability of the membrane to two ions — sodium and potassium — simultaneously.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 6, pp. 637–644, November–December, 1978.     

The role of calcium in prolonged modification of a GABAergic synapse.

Caudal hair cell impulses cause postsynaptic inhibition of ipsilateral type B photoreceptors in the snail Hermissenda. This inhibition is shown to be GABAergic according to a number of criteria. HPLC, mass spectrophotometric, and immunocytochemical techniques demonstrated the presence of GABA in the hair cells and their axons. GABA agonists and antagonists mimic and block the synaptic effect in a manner consistent with endogenous GABAergic transmission. Other properties, including I-V relations, conductance changes and reversal potentials, are comparable for exogenous GABA responses and endogenous effects of the hair cell impulses. This inhibitory synapse has been found to undergo a long-lasting transformation into an excitatory synapse if GABA release is paired with post-synaptic depolarization. GABA, via GABAA and GABAB receptors in the B cell, causes the opening of calcium sensitive chloride and potassium channels that leads to the post-synaptic hyperpolarization. GABA also induces a long-lasting intracellular calcium elevation at the terminal branches of the B cell that greatly outlasts the voltage responses. Synaptic transformation induced by pairings is caused by a decrease in both GABA induced chloride and potassium conductances in the post-synaptic B cell, as well as a significant prolongation of the intracellular calcium accumulation in the B cell's terminal axonal branches.     

A Search for Receptors Modulating the Release of γ-[3H]Aminobutyric Acid in Rabbit Caudate Nucleus Slices

Various putative striatal transmitters and related compounds were studied for their effects on the release of gamma-aminobutyric acid (GABA) from slices of the head of the rabbit caudate nucleus. The slices were preincubated with [3H]GABA and then superfused and stimulated electrically at 5 or 20 Hz. Aminooxyacetic acid was present throughout. The main changes observed were the following. The basal and, less consistently, the electrically evoked overflow of [3H]GABA were enhanced by 3,4-dihydroxyphenylethylamine (dopamine), an effect not blocked by cis-flupentixol or domperidone and not mimicked by apomorphine and D1-selective agonists. The electrically evoked overflow was diminished by 5-hydroxytryptamine (serotonin); the inhibition was prevented by methiothepin. The basal but not the electrically evoked overflow was enhanced by carbachol; acetylcholine and nicotine also accelerated the basal outflow whereas oxotremorine caused no consistent change; the effect of carbachol and acetylcholine were blocked by hexamethonium but not by atropine or by tetrodotoxin. These findings indicate that the GABA neurons in the caudate nucleus may be stimulated by dopamine, although the receptor type involved remains unclear; inhibited by serotonin; and stimulated by acetylcholine acting via a nicotine receptor. However, all drug effects observed were relatively small. No evidence was obtained for autoreceptors, alpha 2-adrenoceptors or receptors for opioids, adenosine or substance P at the GABA neurons.     

Effects of furosemide on neural mechanisms in aplysia

The effects of furosemide on action potentials and responses to several neurotransmitters have been studied in the neurons of Aplysia. Furosemide (10^?7 and 10^?3M) does not visibly affect the normal action potential in R15 neurons. However, when TTX (30μM) is used to block the sodium component in R15, the remaining spike (presumably the calcium component) is increased in amplitude in the presence of furosemide. Furosemide also alters transmitter-induced conductances. Furosemide greatly reduces the amplitude and shifts, in a depolarizing direction, the reversal potential of chloride-dependent responses to γ-aminobutyric acid (GABA) and acetylcholine (ACh). This suggests that furosemide both blocks the chloride channel and inhibits a chloride pump. ACh-induced sodium responses were also reduced by furosemide but to a lesser extent than chloride responses. The potassium response to ACh and a voltage-dependent calcium response to serotonin were not altered. These results indicate that furosemide could alter synaptic responses both presynaptically by enhancement of calcium flux during the action potential and postsynaptically by blockade of chloride and sodium conductances.     

GABA-mediated synaptic inhibition of projection neurons in the antennal lobes of the sphinx moth,Manduca sexta

Responses of neurons in the antennal lobe (AL) of the moth Manduca sexta to stimulation of the ipsilateral antenna by odors consist of excitatory and inhibitory synaptic potentials. Stimulation of primary afferent fibers by electrical shock of the antennal nerve causes a characteristic IPSP-EPSP synaptic response in AL projection neurons. The IPSP in projection neurons reverses below the resting potential, is sensitive to changes in external and internal chloride concentration, and thus is apparently mediated by an increase in chloride conductance. The IPSP is reversibly blocked by 100 microM picrotoxin or bicuculline. Many AL neurons respond to application of GABA with a strong hyperpolarization and an inhibition of spontaneous spiking activity. GABA responses are associated with an increase in neuronal input conductance and a reversal potential below the resting potential. Application of GABA blocks inhibitory synaptic inputs and reduces or blocks excitatory inputs. EPSPs can be protected from depression by application of GABA. Muscimol, a GABA analog that mimics GABA responses at GABAA receptors but not at GABAB receptors in the vertebrate CNS, inhibits many AL neurons in the moth.     

Amoxapine inhibition of GABA-stimulated chloride conductance: investigations of potential sites of activity

Amoxapine inhibits GABA-stimulated chloride conductance by acting on the GABAA-receptor chloride-ionophore complex which can be studied using membrane vesicles prepared from rat cerebral cortex. Amoxapine produces a right shift in the GABA concentration-response curve for the stimulation of 36Cl- uptake into these vesicles with no apparent change in the maximum response. Schild analysis of these data gave a pA2 value of 5.52 with a slope of 0.79. Amoxapine inhibits the binding of the GABAA receptor selective antagonist [3H]SR 95531 with an IC50 value of 3.45 microM and a pseudo Hill coefficient of 0.83. In contrast, 10 microM amoxapine inhibits [3H]flunitrazepam binding by less than 25% while the benzodiazepine antagonist Ro 15-1788 reduces the amoxapine inhibition of GABA-stimulated chloride conductance only at high concentrations. These data suggest that amoxapine does not inhibit chloride conductance by acting as a benzodiazepine inverse agonist and either acts directly on the GABAA receptor as an antagonist or blocks GABA activity at a site closely coupled to it. The ability of amoxapine to inhibit GABA-stimulated chloride conductance is a likely explanation for its proconvulsant activity observed at high doses.     

Modulation of In Vivo Striatal Transmitter Release by Nitric Oxide and Cyclic GMP

Abstract: The effects of nitric oxide (NO) and cyclic GMP on in vivo transmitter release in the rat striatum were investigated using microdialysis sampling in urethane-anaesthetised animals. The NO release-inducing substances S -nitrosoacetylpenicillamine (SNAP), S -nitrosoglutathione (SNOG), and sodium nitroprusside (SNP) increased extracellular concentrations of aspartate (Asp), glutamate (Glu), γ-aminobutyric acid (GABA), taurine (Tau), acetylcholine (ACh), and serotonin (5-HT). Dopamine (DA) concentrations were decreased by SNAP but were increased by SNOG and SNP. An NO scavenger, haemoglobin, blocked or reduced the effects of SNAP on transmitter release. However, the control carrier compounds for SNAP, SNOG, and SNP (penicillamine, glutathione, and potassium ferricyanide, respectively, which do not induce release of NO) also increased GABA, Tau, DA, and 5-HT concentrations. When NO gas was given directly by dissolving it in degassed Ringer's solution, DA concentrations decreased significantly, and those of Asp, Glu, GABA, Tau, ACh, and 5-HT increased. These effects of NO gas were all inhibited by coadministration of haemoglobin and for GABA, Tau, ACh, and DA showed some calcium dependency. The cyclic GMP agonists 8-bromo-cyclic GMP and dibutryl-cyclic GMP stimulated dose-dependent increases in Asp, Glu, GABA, Tau, ACh, DA, and 5-HT concentrations. Increased striatal transmitter release in response to NO may therefore be mediated by its stimulatory action on cyclic GMP formation. NO inhibition of DA release may be mediated indirectly through its stimulation of local cholinergic and GABAergic neurones.     

Comparison of release of endogenous dopamine and γ-aminobutyric acid from rat caudate synaptosomes

Release of endogenous dopamine (DA) and -aminobutyric acid (GABA) from superfused rat caudate synaptosomes was monitored with liquid chromatography with electrochemical detection. Dopamine was analyzed by oxidative detection following alumina extraction while GABA was analyzed with reductive detection following pre-column derivatization with trinitrobenzenesulfonic acid and extraction. Both spontaneous and K⁺-stimulated (40 mM) release were examined as well as the effect of several possible neuromodulatory agents (DA, GABA, muscimol, ascorbic acid, acetylcholine). The content of GABA in the sample and the amount released by K⁺ were approximately fifty times those of DA although the relative amounts released by repetitive K⁺ stimulations were similar. Muscimol and DA significantly attenuated both the spontaneous and stimulated release of GABA while ascorbate and acetylcholine had no effect. Acetylcholine significantly increased both the stimulated and spontaneous release of DA while the other agents had no effect. Dopamine showed an absolute dependence on calcium for stimulated release while GABA exhibited a significant calcium-independent release. These results indicate that profound differences exist in the factors which modulate the release of endogenous DA and GABA.     

Characterization of a depolarizing dopamine response in a vertebrate neuronal somatic cell hybrid

The physiology and pharmacology of a depolarizing dopamine response was studied in the vertebrate neuronal somatic cell hybrid TCX11. The average resting membrane potential was ?50 mV (S.D. = ±7) with a membrane resistance of 40.5 mOhms (S.D. = ±8) as determined from intracellular recordings. Depolarizing current pulses did not elicit an action potential. Cells displayed a linear current-voltage relationship when artificially depolarized up to +30 mV. Iontophoretically applied dopamine elicited a depolarizing response with a conductance increase and a reversal potential of ?15 mV (S.D. = ±4.7). Experiments altering medium ion concentrations demonstrated the conductance increase was to sodium and most likely potassium. The dopamine agonist ET495 (Piribedil) and the analogue epinine mimicked dopamine, while closely related biogenic amines, with the exception of noradrenaline, elicited no response. Apomorphine also elicited a depolarizing response but was much less efficacious than Piribedil. Noradrenaline was less potent than dopamine and appeared to act at the dopamine receptor. Methylation (3-methoxytyramine) or absence of the 3-hydroxy group (tyramine) of dopamine resulted in total loss of activity. The dopamine antagonists chlorpromazine, trifluoperazine, promazine, and bulbocapnine reversibly blocked the response to dopamine at medium concentrations less than 5 μM. The adrenergic antagonist phentolamine blocked the response while phenoxybenzamine only reduced the response at higher concentrations. The acetylcholine antagonists α-bungarotoxin, hexamethonium, and scopolamine did not block the dopamine response. Both d-tubocurarine and atropine acted as antagonists. Collectively, these results demonstrate the presence of a receptor on a cultured cell line that is specific for dopamine, mediates a depolarizing and conductance increase response to dopamine, and displays the pharmacology most closely associated with dopamine receptors.     

鸡视网膜甘氨酸受体、乙酰胆碱受体及离子通道在两栖类卵母细胞中的表达和初步研究

利用两栖类卵母细胞表达鸡视网膜ｍＲＮＡ,借助电压箝方法研究鸡视网膜中的神经递质受体和离子通道、结果表明,鸡视网膜中存在甘氨酸受体和Ｎ型的乙酰胆碱受体。但天冬氨酸和５－ＨＴ、多巴胺未能诱导电流反应。此外还检测到电压依赖性的离子流,主要为延迟整流型的外向钾电流和快速的内向钠电流。     

On the mechanism by which dopamine inhibits prolactin release in the anterior pituitary

An $\text{in}$$\text{vitro}$ perfusion system was used to assess the effects of chloride channel blockers, dopamine (DA) receptor agonists and antagonists, and GABA receptor agonists and antagonists on prolactin release from the mouse anterior pituitary. Dopamine and muscimol inhibited prolactin release ($\text{IC}{}_{50}{}^1\text{= 6 × 10}{}^{\mathrm{?8}}\text{M and}\text{10}{}^{\mathrm{?5}}\text{M}$ respectively). The GABA receptor antagonist bicuculline blocked the inhibition of prolactin release by muscimol but not dopamine. The dopamine receptor antagonist chlorpromazine blocked the dopamine- but not muscimol-induced inhibition of prolactin release. Haloperidol, however, reversed both the muscimol and dopamine induced inhibition of prolactin release. Furthermore, the chloride channel blocker picrotoxinin blocked the inhibition of prolactin release elicited by both dopamine and muscimol. These later results suggest that the anterior pituitary dopamine receptor which mediates the inhibition of prolactin release may be coupled to a picrotoxinin sensitive chloride ionophore and that haloperidol may affect the function of both DA and GABA receptors in the anterior pituitary.     

Perisomatic GABA release and thalamocortical integration onto neocortical excitatory cells are regulated by neuromodulators

Neuromodulators such as acetylcholine, serotonin, and noradrenaline are powerful regulators of neocortical activity. Although it is well established that cortical inhibition is the target of these modulations, little is known about their effects on GABA release from specific interneuron types. This knowledge is necessary to gain a mechanistic understanding of the actions of neuromodulators because different interneuron classes control specific aspects of excitatory cell function. Here, we report that GABA release from fast-spiking (FS) cells, the most prevalent interneuron subtype in neocortex, is robustly inhibited following activation of muscarinic, serotonin, adenosine, and GABA(B) receptors--an effect that regulates FS cell control of excitatory neuron firing. The potent muscarinic inhibition of GABA release from FS cells suppresses thalamocortical feedforward inhibition. This is supplemented by the muscarinic-mediated depolarization of thalamo-recipient excitatory neurons and the nicotinic enhancement of thalamic input onto these neurons to promote thalamocortical excitation.     

The inhibitory effect of strophanthidin on secretion by the isolated gastric mucosa

The unidirectional fluxes of Na⁺ and Cl^- were measured across the isolated gastric mucosa of the bullfrog (R. catesbiana). The addition of strophanthidin, a cardiac aglycone, resulted in marked reductions of the spontaneous potential and short-circuit current. Associated with these changes, the isolated gastric mucosa ceased secreting chloride and hydrogen ion. Although the active component of chloride transfer was inhibited, the exchange diffusion component seemed to increase. No significant changes in membrane conductance or sodium flux were noted. Possible mechanisms of strophanthidin inhibition were discussed in view of its effect on chloride transport across the gastric mucosa and on sodium and potassium transfer in other tissues. It was concluded that the cardiac glycosides may not be specific inhibitors of sodium and potassium transport. This non-specific inhibition suggests that active chloride transport is affected by strophanthidin directly and/or anion secretion is dependent upon normal functioning of cation transport systems in the tissue.     

Effects of various experimental manipulations on neostriatal acetylcholine and dopamine release

The release of endogenous acetylcholine and dopamine and the appearance of their metabolites, choline and dihydroxyphenylacetic acid (DOPAC), from neostriatal slices prepared from Fischer 344 rats was examined under various experimental conditions. There was a dose-dependent increase in the amount of neurotransmitter or metabolite as the medium potassium concentration was increased from 5 to 50 mM. Over an eight minute period in Krebs Ringer bicarbonate buffer containing 25 mM potassium, the rate of release of acetylcholine was 6 to 13 times greater than that of dopamine. The dopamine endogenous to the slice preparation appeared to have little effect on the release of endogenous acetylcholine since manipulations that significantly altered dopamine release (depletion with 6-hydroxydopamine or uptake inhibition with nomifensine) had minimal effects on the cholinergic neurons. In contrast, increasing the endogenous acetylcholine in the preparation by inhibiting acetylcholinesterase resulted in a 1.2 to 12 fold increase in dopamine release depending upon the incubation time and the potassium concentration. These studies indicate that within the neostriatal slices there is minimal influence of the endogenous dopamine on the cholinergic neurons, whereas the extracellular acetylcholine can influence dopamine release when its concentration is increased by inhibition of acetylcholinesterase.     

Localization and pharmacology of some dopamine receptor complexes in the striatum and the pituitary gland: synaptic and son-synaptic communication

The striatum receives massive dopaminergic projections from neurons in the ventral tegmental area, the substantia nigra and the retro-rubral cell group. Dopaminergic neurons in the arcuate nucleus and periventricular hypothalamic nuclei project to the median eminence and the neuro-intermediate lobe of the pituitary gland. The anterior lobe of the pituitary gland is not innervated by dopaminergic neurons, but receives dopamine via a vascular route from the median eminence. Two categories of dopamine receptors (D-1 and D-2) can be identified on the basis of the ability of various drugs to discriminate between these two entities. Dopamine stimulates both D-1 and D-2 receptors. The affinity of dopamine for the D-2 receptor is approximately 1000 times higher than for the D-1 receptor. Dopamine is involved in synaptic as well as non-synaptic communication. Examples of non-synaptic communication via D-2 receptors are the dopamine induced inhibition of prolactin release from the anterior pituitary gland and most likely the D-2 receptor mediated inhibition of the release of acetylcholine in the striatum. Examples of synaptic communication have been found in the striatum where (with ultrastructural techniques) synaptic contacts between dopaminergic nerve terminals and elements from cells containing GABA, substance P or enkephalin have been demonstrated. It is tempting to speculate that synaptic and non-synaptic communication occurs via D-1 and D-2 receptors respectively.     

Voltage-dependent actions of endogenous and exogenous serotonin on identified neurones

1. Impulse activity in an identified serotonin-containing neuron (GSN) produces a slow excitatory synaptic response in another identified neuron, the A neuron. An axon process can be traced close to the follower neuron perikaryon after Lucifer Yellow injection of the GSN perikaryon. 2. The synaptic response is markedly voltage-sensitive being increased at depolarized potentials and almost abolished and not inverted at potentials in excess of about -55mV. 3. Serotonin locally applied produces a similar response. 4. The response to serotonin does not involve a change in conductance to either sodium or chloride ions, but calcium ions do appear to be important either because of their influence on potassium ion permeability or in a direct transfer of charge across the membrane. 5. Another follower neuron exhibits a complex GSN-induced synaptic response comprising a slow potential similar to that seen in the A neuron and also a fast, probably sodium dependent, potential. 6. In addition to producing a weak direct excitation of the A neuron, GSN-activation can also partly reverse accommodation and also prolong the duration of the impulse in the A neuron. 7. Exogenously applied serotonin produces a similar voltage-dependent inward current response in the GSN as seen in the A neuron. It is suggested that the receptors mediating the response on the GSNs may normally be involved in feedback regulation. 8. Cyproheptadine (reversibly), methergoline, mianserin and propranolol (all irreversibly) antagonised the response in the GSN. These agents probably all have action on the ionic mechanism underlying the serotonin response.