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An examination of the outward- and inward-going responses to the two amino acids reveals that, when the holding potential is fixed on either side of (but equidistant from) ECl, the inward and outward currents elicited by glutamate are of equal amplitude, whereas the inward current elicited by GABA is always smaller than the outward current. This was shown to be true in both cell types. In Figure 1, A and B, the response recorded at a holding potential more negative than ECl has been multiplied by
The Journal of Neuroscience, December 1, 2000, 20(23):8585-8596
Independence of and Interactions between GABA-, Glutamate-, and Acetylcholine-Activated Cl Conductances in Aplysia Neurons
JacSue Kehoe1 and Catherine Vulfius2 1 Laboratoire de Neurobiologie, Ecole Normale Supérieure, Paris 75005, France, and 2 Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142292, Russia
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
In certain Aplysia neurons, glutamate, GABA, and acetylcholine (ACh) all elicit desensitizing Cl-dependent responses. This fact and the finding that the glutamate and GABA responses "cross-desensitize" led to the suggestion (Swann and Carpenter, 1975
; King and Carpenter, 1987
This hypothesis is incompatible with the demonstration given here that the GABA- and glutamate-gated channels are clearly distinct; the GABA channel, but not the glutamate channel, shows outward rectification (Matsumoto, 1982
The cross-desensitization was found to be exclusively attributable to the ability of GABA to interact with the glutamate receptor (Oyama et al., 1990
The invertebrate glutamate-gated Cl channels that have been cloned resemble the vertebrate glycine receptor (Vassilatis et al., 1997
Key words: GABA; glutamate; acetylcholine; cross-desensitization; chloride channel; Aplysia; mollusk; neuron; pharmacological characteristics; sulfate
INTRODUCTION
A number of studies on vertebrate neurons have described interactions between inhibitory Cl responses elicited by GABA, glycine, and
-alanine, e.g., between responses to GABA and glycine (Barker and McBurney, 1979
In invertebrates, many different neurotransmitters, including glutamate but not glycine, gate Cl channels. In cells in which different transmitters activate Cl conductances, interactions observed between the responses have led to the suggestion that different transmitters share the same receptor molecule. For example, in crayfish muscle, a single Cl channel is activated by similar concentrations of glutamate, GABA, and acetylcholine (ACh) (Franke et al., 1986
In the present study, we have reexamined the interactions between the glutamate-, GABA-, and ACh-activated responses in Aplysia neurons. By exploiting our finding that the GABA-gated channel has distinguishing characteristics and the fact that, in certain cells, only one of the relevant receptors is expressed, we have shown that all three of these transmitters open Cl channels by binding to distinct and independent molecular entities. Nevertheless, interactions were shown to exist between the GABA and glutamate responses. These seemingly bi-directional interactions can be entirely explained by the ability of GABA to interact with the glutamate receptor (Oyama et al., 1990
MATERIALS AND METHODS
Experimental preparation. The experiments described in this paper were performed on cells from either the buccal, pleural, or cerebral ganglia of Aplysia.
The ganglia were prepared as described previously (Kehoe, 1985
Electrodes, voltage clamp, recording procedures, and treatment of data. For experiments illustrated in Figures 2A-C, 3B, 4B, 6C, and 10A, whole-cell patch-clamp methods (Hamill et al., 1981
ensured a good exchange, and data were retained only from cells for which the access resistance remained constant throughout the experiment. In all other experiments, recordings were made in conventional microelectrode voltage clamp using hand-pulled microelectrodes made with a de Fonbrune microforge and filled with 0.5 M K2SO4. Although cells with intact axons were used in these experiments, and obviously the voltage in much of the axon was not controlled by the somatically placed electrodes, clamp error cannot explain the changes in response amplitude studied in these experiments. No evidence of a failure to control somatic voltage was seen in the voltage traces, and the control of the somatic voltage was evident from the unchanging amplitude of one of the two agonist-induced responses in experiments in which the other agonist response was markedly reduced. Activation of axonal membrane was minimized by the somatic application of the agonist and by its rapid removal by the flow from the control tube, as well as by a continual superfusion of the entire ganglion. For an additional description of the characteristics of the two-electrode voltage clamp, see Kehoe (1985)
Continuous recordings were made on a Servogor 340 paper recorder and on a digital audio tape recorder. Records of currents elicited by agonist applications were digitized and sampled on-line on a Dell (Round Rock, TX) computer, via a Cambridge Electronic Design (Cambridge, UK) 1401 interface, using the Whole Cell Eectrophysiology program from Strathclyde Electrophysiological Software.
External and internal solutions. The artificial seawater (ASW) bathing the ganglion contained (in mM): 480 NaCl, 10 KCl, 10 CaCl2, 50 MgCl2, and 10 Na-HEPES, pH 7.8. The internal solution used in the whole-cell clamp experiments illustrated here contained (in mM): 411 K2SO4, 8.3 Na2SO4, 1 CaCl2, 2 MgCl2, and 1.5 EGTA, buffered with 20 K-HEPES to pH 7.4. In a few nonillustrated experiments, a KCl-based solution was used to show that the relevant factor causing the diminution of the GABA response in whole-cell perfusion experiments came from the presence of sulfate ions in the internal solution. The KCl-based internal solution contained (in mM): 496 KCl, 10 NaCl, 2 MgCl2, 1 CaCl2, 1.5 EGTA, and 20 K-HEPES, pH 7.4.
Fast application system. The fast application system used here has been described previously in detail (Johnson and Ascher, 1987
The duration of agonist application in all experiments was 2 sec, and the interval between applications was 1 min. Because in most experiments there was an alternation between two different agonists (e.g., GABA and glutamate), for a given agonist, a 2 min interval separated two successive applications. With the agonist concentrations used here, this regimen yielded control responses of a constant amplitude. The antagonists were applied only through the control tube (see exception in Fig. 9A). This implies that, during the 2 sec application of the agonist, a partial wash of the preapplied antagonist occurs. The application of desensitizing agonists through the control tube resulted in a similar partial wash during the 2 sec agonist application. This led, at some concentrations, to particularities in the recorded currents that are discussed in the relevant text describing the figures.
Drugs. GABA, L-glutamic acid (monosodium salt), ACh,
Experimental n values, statistical analyses, and experimental controls. Each conclusion that has been illustrated in this paper was drawn from a minimum of three experiments (with the exception of that illustrated in Fig. 2B, for which only two experiments were performed). Statistical analyses using either the ANOVA test (Figs. 1C, 8) or the Student's t test (other figures) quantified the effects of the various manipulations on the responses to the different agonists.
RESULTS
Comparison of glutamate- and GABA-gated Cl responses
Glutamate, GABA, and ACh each elicits a rapidly activated inhibitory response in a number of neurons in Aplysia central ganglia. In a given experiment and at a given time, the reversal potential of this response is the same for all three of the transmitters and has been shown, for the response to ACh, to be equal to the Cl equilibrium potential (Kehoe, 1972a
A given molluscan neuron often expresses more than one receptor type for a given transmitter. That is the case for glutamate in the medial cells studied here, because, in addition to gating a Cl channel in those cells, glutamate also activates a nonspecific cationic channel, thereby eliciting a two-component response (King and Carpenter, 1987
Differential voltage dependence of the glutamate- and GABA-gated Cl conductances
Examples of the responses to glutamate and GABA in the two different cell types are shown in Figure 1. In the medial cells (Fig. 1A), it can be seen that the Cl current elicited by glutamate (outward at26 mV, inward at
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Figure 1. Differential voltage dependence of glutamate- and GABA-activated Cl conductances measured in two-electrode voltage clamp in medial and buccal cells. A, Glutamate and GABA responses in a medial cell. Glutamate elicited a two-component response consisting of a rapidly desensitizing cationic element (seen here as an inward current at all holding potentials) and an inhibitory, Cl-dependent element that is manifested by an outward current at 0.0001 and that of the observed main effect of voltage is p
Differential effect of intracellular sulfate ions on the glutamate and GABA responses
The differential voltage dependence of the Cl conductances activated by glutamate and GABA suggests that the two transmitters gate different types of Cl channels. This impression was reinforced by the differential effect of intracellular sulfate ions observed here on the responses to GABA and glutamate. The experiments illustrated in Figure 2A-C were performed in whole-cell patch-clamp mode, so the solution in the pipette was constantly exchanging with the cytoplasm, hence altering the internal Cl concentration and thereby provoking changes in ECl. Consequently, in Figure 2, A and B, periodic adjustments throughout the experiments were made to ensure that the holding potential remained at a constant distance from ECl. Under these conditions, the amplitude of the glutamate response remained constant (mean of six experiments was 99.1% of control;= 2.13%), whereas that to GABA decreased progressively to an average of 37.7% of the control value (
Figure 2C illustrates another protocol for studying the differential effect of internal sulfate ions on the GABA and glutamate responses. In this experiment, the holding potential was held constant while ECl became more negative because of the whole-cell perfusion. Because of the resulting increase in driving force for Cl ions, the response to glutamate increased, whereas, despite the change in driving force, the response to GABA decreased. This simplified protocol, which of course leads to the same conclusion, was used in experiments to be described later evaluating differential effects of intracellular sulfate on responses elicited by various agonists. It is known that GABA responses in some mammalian neurons show rundown when intracellular ATP is washed out by whole-cell perfusion (Shirasaki et al., 1992
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Figure 2. Selective blockade by sulfate ions of the GABA-induced Cl-dependent response. A, Whole-cell recording with K2SO4-based internal solution in a buccal cell. The membrane potential was maintained at 15 mV less negative than ECl. Whole-cell perfusion with a sulfate-containing internal solution caused a selective diminution of the GABA-induced Cl-dependent response. From six experiments in which the effect of sulfate was measured 20 min after control responses, the glutamate response was maintained at 99.1% of control (
Pharmacological distinctions between the glutamate and GABA responses
One of the factors that has held back the identification of glutamatergic and GABAergic synapses in molluscan nervous systems is the paucity of pharmacological tools that have been found to be selective for the different Cl-dependent responses activated by these different transmitters. In an effort to distinguish further between the glutamate- and GABA-induced Cl responses and to provide compounds that could eventually assist in identifying synapses using these neurotransmitters, a number of potential agonists and antagonists were evaluated.
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Figure 3.
TACA
The GABA analog TACA activates a conductance that, like that activated by GABA, is voltage-dependent (Fig. 4A) and is blocked by intracellular sulfate ions (Fig. 4B). Furthermore, TACA (100 µM) preferentially desensitizes-blocks the GABA response (Fig. 4C) (Fig. 4A-C, see legend for statistical analyses of the findings illustrated).
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Figure 4. TACA selectively activates the GABA receptor in the buccal and medial cells. A, Responses of a buccal cell to glutamate and TACA measured with a two-electrode voltage clamp at 17 mV on either side of ECl. Note that the amplitude of the TACA-induced currents measured at 17 mV on either side of ECl are not of equal amplitude, with the TACA-induced inward current being smaller than the TACA-induced outward current. The inward and outward currents elicited by glutamate at the same holding potentials are of equal amplitude (mean inward to outward current for glutamate was 102% with
Hypotaurine
Hypotaurine, an endogenous amino acid shown to have inhibitory effects in cerebellar slices (Okamoto and Sakai, 1981
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Figure 5. Preferential block of the glutamate Cl-dependent response by hypotaurine and preferential block-desensitization of the GABA Cl-dependent response by CACA. A, Effect of 1 mM hypotaurine on equal amplitude responses of a medial cell to 1 mM glutamate and 500 µM GABA measured in two-electrode voltage clamp at 17 mV on either side of ECl. Note that hypotaurine, which induced no change in holding potential, preferentially blocked the glutamate-induced response. The glutamate response was reduced to 20.2% (
CACA
CACA, an agonist of GABAC vertebrate receptors (Johnston, 1996Differential expression of GABA and glutamate receptors in different cells
Cells in which the glutamate but not the GABA receptor is expressed reveal that GABA can activate the glutamate receptor
In a group of small identifiable cells in the right pleural ganglion (Ascher et al., 1978
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Figure 6. Recordings of glutamate and GABA responses in cells from an identifiable group situated near the pleural-pedal connective in the right pleural ganglion (Ascher et al., 1978
As was seen in Figure 6A, GABA activation of the glutamate receptor yields a response that is much smaller than that elicited by the same concentration of glutamate (for n = 3, the average response to 1 mM GABA is 3.83% that of the response to 1 mM glutamate). Nevertheless, there appears to be little difference in the concentrations of the two amino acids needed to elicit a threshold response via the glutamate receptor. When testing 20 and 50 µM glutamate and 20 and 100 µM GABA on the pleural cells, no response could be elicited with 20 µM of either agonist. A response was elicited by 50 µM glutamate in all five cells (average of 1268 pA), whereas 100 µM GABA elicited a response (average of 142 pA) in four of the five cells. The fifth cell responded to 200 µM, the next higher concentration tested.
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Figure 7. The effect of pharmacological compounds shown to act on either the glutamate- or GABA-induced Cl-dependent responses confirm that the response to GABA in the small pleural cells (Ascher et al., 1978
GABA activation of the glutamate receptor explains the observation of cross-desensitization
Cross-desensitization between transmitter-activated Cl channels has been described frequently in both vertebrate and invertebrate preparations (invertebrate, Franke et al., 1986
It should be mentioned at this point that changes in ECl cannot account for the GABA-induced diminutions in the amplitude of the glutamate response: (1) ECl was continually monitored, and evaluations of the glutamate response were always made at a holding potential of a constant distance from ECl; (2) application of GABA had the same desensitizing effect on the glutamate response at ECl and at less negative potentials; (3) GABA had a marked desensitizing effect at concentrations that elicited no current in the cell in which the glutamate responses were being evaluated; and (4) in many neurons (e.g., the medial cells), whereas a Cl current gated by the GABA receptor blocked the glutamate response, a similar Cl current gated by the glutamate receptor failed to affect the GABA response. Likewise, it should be pointed out that an action of GABA on presynaptic neurons can be rejected as a possible source for the cross-desensitization effect. A number of similar experiments (data not shown) performed here on isolated cells in culture confirmed completely the findings from cells in the intact ganglion. Furthermore, the experiments of King and Carpenter (1987)
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Figure 8. Effect of GABA on the response of a pleural cell to 1 mM glutamate recorded in two-electrode voltage clamp. Increasing concentrations of GABA (1, 10, and 100 µM) applied successively through the control tube caused an increasing diminution in the response of a pleural cell to 1 mM glutamate. Notice that no GABA-induced change in holding potential can be detected. The cell was held at 20 mV less negative than ECl. See Results for a detailed résumé of related experiments. The response to 1 mM glutamate in 1 µM GABA was reduced to 85.1% of the control amplitude (
Cells in which the GABA but not the glutamate receptor is expressed reveal that glutamate cannot activate the GABA receptor
There are identifiable cells in the cerebral ganglion in which GABA, but not glutamate, elicits a Cl-dependent response. The response to glutamate in these cells is a pure cationic one and that to GABA is a pure Cl-dependent one, as illustrated in Figure 9A, first column. Although, as has been shown above, GABA can effectively activate (Figs. 6, 7) and block (Fig. 8) the glutamate Cl-dependent response, the opposite is not true. In Figure 9A, glutamate added to the control tube completely desensitized the glutamate excitatory response in the cerebral cells but had no effect on the GABA Cl-dependent response (Oyama et al., 1990
The failure of glutamate to block the Cl-dependent response to GABA can also be seen in the medial cells in which both glutamate and GABA receptors mediating Cl-dependent responses are expressed (Fig. 9B) (mean response to 1 mM GABA in the presence of 1 mM glutamate for four experiments was 102% of control;
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Figure 9. The Cl-dependent response to GABA measured in two-electrode voltage clamp in a cerebral cell (A), a medial cell (B), and a buccal cell (C, C') in the absence or presence of glutamate. A, In the cerebral cell control records, GABA elicits a pure Cl-dependent response (top trace), whereas glutamate elicits a pure cationic current (bottom trace). Glutamate (10 mM) flowing through the control tube (middle column) desensitized the glutamate cationic current but failed to affect the GABA response. The inward-going current seen on the downswing of the GABA response (middle GABA record) reveals a recovery from desensitization of the glutamate cationic response, elicited here by the glutamate flowing from the control tube at the end of the 2 sec application of the glutamate-free, 1 mM GABA solution. In the third column, it can be seen that, even when 10 mM glutamate was added to the 1 mM GABA solution, there was no blocking effect of glutamate on the GABA response. Note that the response to the glutamate-GABA agonist application is biphasic, consisting of a cationic response elicited by 10 mM glutamate and a Cl-dependent response elicited by 1 mM GABA. B, Responses to GABA (top trace) and glutamate (bottom trace) recorded from a medial cell in the absence and presence of 100 µM or 1 mM glutamate flowing through the control tube. Note that both the cationic and Cl-dependent response to glutamate were desensitized by the glutamate in the control tube, whereas no desensitizing or blocking effect of the glutamate can be detected on the response to GABA. The presence of 1 mM glutamate in the control tube can be detected on the downswing of the GABA response (final record in B) because the return of the control tube containing 1 mM glutamate elicited a weak cationic current after the 2 sec application of glutamate-free GABA-containing solution. C, Responses of a buccal cell to glutamate and GABA. C', Effect of the application of 100 µM glutamate in the control tube on the response of the buccal cell to GABA. Note that the atypical decay of the GABA response, i.e., a change in rate of desensitization at the end of the 2 sec application, disappeared in the presence of 100 µM glutamate, presumably because glutamate desensitized the element of the GABA response that was mediated by the glutamate receptor (Difference).
In cells in which the glutamate receptor is highly expressed, the response to 1 mM GABA often contains a detectable component mediated by the glutamate receptor
In light of the finding that GABA can activate the glutamate receptor (Figs. 6, 7), it is interesting to turn our attention to the differences in kinetics of the response to 1 mM GABA in the medial versus buccal neurons. The expression of the glutamate-gated Cl channel is much greater in the buccal than in the medial cells, with the response to 1 mM glutamate being typically approximately twice that to 1 mM GABA in the buccal cells, and vice versa in the medial cells. In the medial cells, the decay of the response to 1 mM GABA is almost always smooth, with no change in rate of decay manifested at the end of the 2 sec GABA pulse (Figs. 1A, 9B). At this concentration, the decay appears to depend exclusively on the "off rate" of the desensitized GABA receptor. That is not the case for the response to glutamate, which shows a sharp change in decay rate when the control flow replaces the agonist flow. In the buccal cells, on the other hand, the response to 1 mM GABA often shows an "atypical" decay (Figs. 1B, 9C). As can be seen in Figure 9C', the "hump" sometimes seen in the GABA response of the buccal cells disappears with a "desensitizing" application of 100 µM glutamate in the control tube, leaving a decay typical of the GABA response mediated by the voltage-dependent, sulfate-sensitive GABA receptor. The transformation in the GABA response in the presence of 100 µM glutamate was evaluated by approximating the integrals of the GABA responses in the presence and absence of 100 µM glutamate and subtracting these integrals. The mean reduction in the control GABA response thus obtained was 10.3% (n = 6;Comparison of the amino acid receptors with the two ACh receptors mediating Cl-dependent responses
It was shown recently by Kehoe and McIntosh (1998)
The ACh-activated conductance, like that activated by glutamate, fails to show a voltage dependence over the range of holding potentials studied here (Kehoe and McIntosh, 1998
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Figure 10. Comparison of the amino acid Cl-dependent responses with the cholinergic Cl-dependent response. A, Recordings from a buccal cell in whole-cell voltage clamp with K2SO4-based internal solution of responses to 500 µM GABA and 500 µM ACh. These records were taken at a holding potential 20 mV less negative than ECl and show that the whole-cell perfusion with a sulfate-containing internal solution selectively diminished the GABA response. B, MLA blocked the ACh-induced Cl-dependent responses at 2 µM but had no effect, even at 10 µM, on the responses to either glutamate or GABA. These responses were recorded from buccal cells in two-electrode voltage clamp. C, C', Neither 1 mM glutamate (C) nor 1 mM GABA (C') added to the control tube affected the response to 200 µM ACh recorded in two-electrode voltage clamp from a buccal cell. The peak ACh response in the presence of 1 mM glutamate was 99.7% of the control (
The pharmacology of the Cl-dependent ACh responses has been described in detail by Kehoe and McIntosh (1998)
-bungarotoxin (Kehoe and McIntosh, 1998
DISCUSSION
The experiments described here have shown that the receptor-channel complexes mediating the Cl-dependent responses to glutamate, GABA, and ACh in Aplysia neurons are independent entities. Nevertheless, cross-desensitization does occur between the GABA and glutamate responses and was shown to result exclusively from the ability of GABA to interact with the glutamate receptor.
These findings are compatible with the results obtained by King and Carpenter (1987)
Glutamate and GABA activation of the glutamate receptor
In our study, the concentrations of GABA and glutamate required for threshold activation of the glutamate receptor were found to be remarkably similar. That is, to consistently obtain a discernible response to glutamate, a concentration of 50 µM was needed; GABA was shown to activate the same receptor at only twice that concentration. In contrast, the average currents elicited by 1 and 10 mM GABA in cells having only the glutamate receptor (Fig. 6A,B) were only ~4 and 36%, respectively, of the response of the same cell to 1 mM glutamate.
The low concentrations of GABA that are able to affect the sensitivity of the glutamate receptor (Fig. 8) suggest that, if both GABA and glutamate receptors are coexpressed on the same subsynaptic membrane, liberation of GABA on that membrane would be able to cross-desensitize the glutamate receptor. The protocol used here did not permit an evaluation of the kinetics of the GABA-induced desensitization. However, from the work of Oyama et al. (1990)
Although the data strongly suggest that direct activation by GABA of the glutamate receptor mediates the cross-desensitization process, the molecular mechanism by which GABA and
Relationship between the invertebrate glutamate receptor and the vertebrate glycine receptor
The invertebrate glutamate receptors gating Cl channels that have thus far been cloned show greater resemblance to the vertebrate glycine receptor than to any other receptor (Cully et al., 1994
A recent study evaluating the differential activation by glycine and GABA of a recombinant homomeric glycine receptor revealed a 200- to 300-fold difference in the EC50 values of the activation curves for the two amino acids (Fucile et al., 1999
receptor, the difference in sensitivity to the two amino acids was much greater, on the order of 10,000-fold (Calvo and Miledi, 1995
In previously published experiments on isolated Aplysia neurons, concentration-response curves were obtained for the glutamate response (Ikemoto et al., 1988b
These studies together suggest a high selectivity of both the vertebrate and invertebrate GABA receptor, whereas both the vertebrate glycine receptor and the invertebrate glutamate receptor show some sensitivity to GABA.
However, many molecular variations of GABA and glycine receptors exist in vertebrate neurons, and this diversity may explain the wide range of findings concerning cross-desensitization between these ligand-gated Cl channels. For example, whereas Choquet and Korn (1988)
A similar diversity must exist in invertebrate neurons because, whereas the glutamate receptor of molluscs is desensitized by even low concentrations of GABA, no interaction between the two amino acid responses is seen in some invertebrate ganglionic neurons (lobster, Cleland and Selverston, 1998
The ACh-activated receptor-channel complex
Although we have no data that permit us to discriminate between the properties of the ACh-gated channel(s) (Kehoe and McIntosh, 1998
GABAA or GABAC?
The object of the pharmacological evaluation of the GABA receptor in this study was primarily to differentiate it from the receptor underlying the glutamate response. However the finding that TACA is a more effective agonist than CACA suggests that the molluscan GABA receptor resembles the GABAC rather than the GABAA receptor (Johnston, 1996
Sulfate blockade of the GABA channel
The observation made here that intracellular sulfate ions selectively block the GABA response was exploited in these experiments as a "tool" for differentiating the GABA receptor-channel complex from the glutamate and ACh receptor-channel complexes, and the means by which this blockade occurs have not as yet been examined. However, the block is clearly independent of voltage over the range tested (Fig. 2B). Furthermore, a differential permeability of the GABA receptor channel to sulfate ions cannot explain its differential sensitivity to internal sulfate. It was shown previously (Kehoe, 1972a
FOOTNOTES Received March 27, 2000; revised Aug. 31, 2000; accepted Sept. 11, 2000.
This research was supported by the Centre National de la Recherche Scientifique (Unité Mixte de Recherche 8544) (to J.K.) and by Université Pierre et Marie Curie Visiting Professorship and INTAS-93-3269 (to C.V.).
Correspondence should be addressed to JacSue Kehoe, Laboratoire de Neurobiologie, Ecole Normale Supérieure, 46, rue d'Ulm, Paris, 75005, France. E-mail: kehoe{at}wotan.ens.fr.
REFERENCES
- Ascher P, Marty A, Neild TO (1978) The mode of action of antagonists of the excitatory response to acetylcholine in Aplysia neurones. J Physiol (Lond) 278:207-235
[Abstract/Free Full Text] .- Baev KV, Rusin KI, Safronov BV (1992) Primary receptor for inhibitory transmitters in lamprey spinal cord neurons. Neuroscience 46:931-941[Web of Science][Medline].
- Barker JL, McBurney RN (1979) GABA and glycine may share the same conductance channel on cultured mammalian neurones. Nature 277:234-236[Medline].
- Boué-Grabot E, Taupignon A, Tramu G, Garret M (2000) Molecular and electrophysiological evidence for a GABAC receptor in thyrothropin-secreting cells. Endocrinology 141:1627-1632
[Abstract/Free Full Text] .- Calvo DJ, Miledi R (1995) Activation of GABA
1 receptors by glycine and
- Choquet D, Korn H (1988) Does
- Cleland TA, Selverston AI (1998) Inhibitory glutamate receptor channels in cultured lobster stomatogastric neurons. J Neurophysiol 79:3189-3196
[Abstract/Free Full Text] .- Cully DF, Vassilatis DK, Liu KK, Paress PS, van der Ploeg LHT, Schaeffer JM, Arena JP (1994) Cloning of an avermectin sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371:707-711[Medline].
- Duan S, Cooke IM (2000) Glutamate and GABA activate different receptors and Cl
[Abstract/Free Full Text] .- Fairman WA, Amara SG (1999) Functional diversity of excitatory amino acid transporters: ion channel and transport modes. Am J Physiol [Review] 277:F481-F486.
- Franke Ch, Hatt H, Dudel J (1986) The inhibitory chloride channel activated by glutamate as well as by
-amino-butyric acid (GABA). J Comp Physiol [A] 159:591-609.
- Fucile S, de Saint Jan D, David-Watine D, Korn H, Bregestovski P (1999) Comparison of glycine and GABA actions on the zebrafish homomeric glycine receptor. J Physiol (Lond) 517:369-383
[Abstract/Free Full Text] .- Gardner D, Kandel ER (1977) Physiological and kinetic properties of cholinergic receptors activated by multiaction interneurons in buccal ganglia of Aplysia. J Neurophysiol 40:333-348
[Abstract/Free Full Text] .- Hamill O, Marty A, Neher E, Sakmann B, Sigworth F (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391:85-100[Web of Science][Medline].
- Hamill OP, Bormann J, Sakmann (1983) Activation of multiple-conductance state chloride channels in spinal neurons by glycine and GABA. Nature 305:805-808[Medline].
- Han MH, Li Y, Yang XL (1997) Desensitizing GABAC receptors on carp retinal bipolar cells. NeuroReport 14:1331-1335.
- Ikemoto Y, Akaike N (1988) The glutamate-induced chloride current in Aplysia neurones lacks pharmacological properties seen for excitatory responses to glutamate. Eur J Pharmacol 150:313-318[Web of Science][Medline].
- Ikemoto Y, Akaike N, Kijima H (1988a) Kinetic and pharmacological properties of the GABA-induced chloride current in Aplysia neurones: a "concentration clamp" study. Br J Pharmacol 95:883-895[Web of Science][Medline].
- Ikemoto Y, Akaike N, Ono K (1988b) Kinetic analysis of glutamate-induced chloride current in Aplysia neurones: a "concentration clamp" study. Eur J Pharmacol 150:303-311[Web of Science][Medline].
- Johnson J, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529-531[Medline].
- Johnston GAR (1996) GABAC receptors: relatively simple transmitter-gated ion channels? Trends Pharmacol 17:319-323[Medline].
- Jonas P, Bischofberger J, Sandkühler J (1998) Corelease of two fast neurotransmitters at a central synapse. Science 281:419-424
[Abstract/Free Full Text] .- Katz PS, Levitan IB (1993) Quisqualate and ACPD are agonists for a glutamate-activated current in identified Aplysia neurons. J Neurophysiol 69:143-150
[Abstract/Free Full Text] .- Kehoe JS (1972a) Ionic mechanism of a two component cholinergic inhibition in Aplysia neurons. J Physiol (Lond) 225:85-114
[Abstract/Free Full Text] .- Kehoe JS (1972b) Three acetylcholine receptors in Aplysia neurones. J Physiol (Lond) 225:115-146
[Abstract/Free Full Text] .- Kehoe JS (1978) Transformation by concanavalin A of the response of molluscan neurones to L-glutamate. Nature 274:866-869[Medline].
- Kehoe JS (1985) Synaptic block of a transmitter-induced potassium conductance in Aplysia neurones. J Physiol (Lond) 369:399-437
[Abstract/Free Full Text] .- Kehoe JS (1994) Glutamate activates a K+ conductance increase in Aplysia neurons that appears to be independent of G proteins. Neuron 13:691-702[Web of Science][Medline].
- Kehoe JS, McIntosh JM (1998) Two distinct nicotinic receptors, one pharmacologically similar to the vertebrate
- Kim KH, Takeuchi H (1990) Pharmacological characteristics of two different types of inhibitory GABA receptors on Achatina fulica neurones. Eur J Pharmacol 182:49-62[Medline].
- King WM, Carpenter DO (1987) Distinct GABA and glutamate receptors may share a common channel in Aplysia neurons. Neurosci Lett 82:343-348[Web of Science][Medline].
- King WM, Carpenter DO (1989) Voltage-clamp characterization of Cl
[Abstract/Free Full Text] .- Krishtal OA, Osipchuk YV, Vrublevsky SV (1988) Properties of glycine activated conductances in rat brain neurons. Neurosci Lett 84:271-276[Web of Science][Medline].
- Lewis CA, Faber DS (1993) GABA responses and their partial occlusion by glycine in cultured rat medullar neurons. Neuroscience 52:83-96[Web of Science][Medline].
- Matsumoto M (1982) The voltage-dependent nature of the GABA-induced conductance change recorded from the ganglion cell of Aplysia. Jpn J Physiol 32:55-67[Medline].
- Okamoto K, Sakai Y (1981) Inhibitory actions of taurocyamine, hypotaurine, homotaurine, taurine and GABA on spike discharges of Purkinje cells, and localization of sensitive sites, in guinea pig cerebellar slices. Brain Res 206:371-386[Web of Science][Medline].
- Oyama Y, Ikemoto Y, Kits KS, Akaike N (1990) GABA affects the glutamate receptor-chloride channel complex in mechanically isolated and internally perfused Aplysia neurons. Eur J Pharmacol 185:43-52[Web of Science][Medline].
- Shirasaki T, Aibara K, Akaike N (1992) Direct modulation of GABAA receptor by intracellular ATP in dissociated nucleus tractus solitarii neurones of rat. J Physiol (Lond) 449:551-572
[Abstract/Free Full Text] .- Swann JW, Carpenter DO (1975) Organisation of receptors for neurotransmitters on Aplysia neurones. Nature 258:751-754[Medline].
- Trombley PQ, Hill BJ, Horning MS (1999) Interactions between GABA and glycine at inhibitory amino acid receptors on rat olfactory bulb neurons. J Neurophysiol 82:3417-3422
[Abstract/Free Full Text] .- Vassilatis DK, Elliston KO, Paress PS, Hamelin M, Arena JP, Schaeffer JM, Van der Ploeg LH, Cully DF (1997) Evolutionary relationship of the ligand-gated ion channels and the avermectin-sensitive, glutamate-gated chloride channels. J Mol Evol 44:501-508[Web of Science][Medline].
- Wu FS, Gibbs TT, Farb DH (1993) Dual activation of GABAA and glycine receptors by
- Zufall F, Franke Ch, Hatt H (1988) Acetylcholine activates a chloride channel as well as glutamate and GABA. J Comp Physiol [A] 163:609-620.
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