Effect of picrotoxin on benzodiazepine receptors and GABA receptors with reference to the effect of Cl− ion

Fujimoto, Masafumi; Okabayashi, Tadashi

doi:10.1016/0024-3205(81)90051-5

Cited by 31 publications

(12 citation statements)

References 13 publications

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“…First, GABA binding might influence the affinity of picrotoxin for its binding site, and, second, picrotoxin binding might initially produce an unblocked-bound state, leading subsequently to a blocked state. That the picrotoxin binding site may interact allosterically with the GABA binding site is also supported by work on vertebrate GABA receptors (Fujimoto & Okabayashi, 1981;Supavilai et al, 1982).…”

Section: Comparison Ofpicrotoxin Sensitivity Among Crustacean Speciesmentioning

confidence: 82%

A GABA‐activated chloride‐conductance not blocked by picrotoxin on spiny lobster neuromuscular preparations

Albert

Lingle

Marder

et al. 1986

British J Pharmacology

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1 Conductance increases to -y-aminobutyric acid (GABA) were recorded in the gm6b and opener muscle of the spiny lobsters, Panulirus interruptus and P. argus. 2 GABA-evoked responses were insensitive to picrotoxin at concentrations as high as 5 x 10-5 M. Some blockade by picrotoxin was observed at higher concentrations. 3 In normal physiological saline, the reversal potential of the Panulirus GABA-induced response was near the resting potential. The reversal potential was unaffected by reductions in sodium and calcium. Reduction of chloride by 50% resulted in a greater than 10 mV shift in the reversal potential of the GABA-induced response. 4 Muscimol was able to mimic the action of GABA while baclofen was without effect. Bicuculline was a weak blocker.5 Avermectin Bla irreversibly increased the chloride permeability of the gm6b membrane. This conductance increase was blocked by picrotoxin over a range of concentrations similar to those required for blockade of the GABA-induced response. 6 GABA-induced responses of the gm6b muscle of Homarus americanus were blocked almost completely by picrotoxin 10-6 M.7 Sensitivity to picrotoxin is not invariably associated with GABA-activated chloride-mediated conductance increases. It is suggested that alteration in the binding-site for picrotoxin on the GABAactivated chloride-ion channel does not change other functional characteristics of the GABA-induced response.

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Section: Comparison Ofpicrotoxin Sensitivity Among Crustacean Speciesmentioning

confidence: 82%

A GABA‐activated chloride‐conductance not blocked by picrotoxin on spiny lobster neuromuscular preparations

Albert

Lingle

Marder

et al. 1986

British J Pharmacology

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“…Changes in the junction potential of the reference electrode were compensated for in determining the membrane potential. Lower [Cl-] was not used since it has been reported that the binding of GABA is Cl-dependent in ligand-binding experiments (Fujimoto & Okabayashi, 1981 Recordings were accepted if the spike height was more than 70 mV, the input resistance was greater than 20 MCI and the resting potential was more negative than -55 mV. Hyperpolarizing current pulses (01-0-2 nA, 100 ms, about 1 Hz) were passed into the cell to estimate changes in input resistance.…”

Section: Methodsmentioning

confidence: 99%

gamma‐Aminobutyric acid hyperpolarizes rat hippocampal pyramidal cells through a calcium‐dependent potassium conductance.

Blaxter¹,

Carlen²,

Davies³

et al. 1986

The Journal of Physiology

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SUMMARY1. Application of y-aminobutyric acid (GABA) to the dendrites of CA1 pyramidal cells in hippocampal slices produced depolarizing and hyperpolarizing responses.2. Picrotoxin (50 ItM) blocked the depolarizing response of the dendrites to GABA but not the hyperpolarizing responses of the dendrites. The hyperpolarizing response of the cell body to GABA was reduced but not blocked by picrotoxin, suggesting the presence of a complex response at the cell body.3. The depolarizing response of the dendrites and the hyperpolarizing response of the cell body appeared to be at least partly Cl-dependent as they were respectively increased and decreased in size in low-Cl-artificial cerebrospinal fluid (ACSF), while the hyperpolarizing response of the dendrites was unaffected.4. The hyperpolarizing response of the dendrites was increased in amplitude in low-K+ ACSF and the extrapolated reversal potential of the response became more negative, suggesting that the response was K+ dependent.5. The hyperpolarizing response of the dendrites was decreased in size in high-K+ ACSF and could be readily inverted by current injection. The reversal potential became less negative in high-K+ ACSF in a similar manner to that of the slow afterhyperpolarization following a train of spikes, indicating that the response was a K+ conductance.6. Perfusion of the slice with normal or 0-Ca2+ ACSF containing Cd2+ or Mn2+ blocked synaptic transmission, increased spike duration and blocked the slow phase of the spike after-hyperpolarization (a.h.p.). This latter potential is thought to be mediated by a Ca2+-dependent K+ conductance. Later, the hyperpolarizing response of the dendrites to GABA was blocked without an effect on the other GABA responses.7. Pressure application of Cd2+ (0-2-2 mM) onto the surface of the slice rapidly reduced or blocked the slow a.h.p. and the dendritic hyperpolarizing response to GABA.8. Intracellular injection of EGTA rapidly blocked the slow phase of the a.h.p. and then later blocked or reduced the dendritic hyperpolarizing response to GABA.T. J. BLAXTER AND OTHERS 9. We conclude that the hyperpolarizing response of the dendrites to GABA is mediated by a Ca2+-dependent K+ conductance.

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“…tivity of GABA at the high-affinity site while concurrently enhancing the coupling of low-affinity site to the benzodiazepine receptor. Since C1-dependency also has been demonstrated for barbiturates , for picrotoxin (Fujimoto and Okabayashi, 1981;Supavilai et al, 1982a), and for SQ 20009 and SQ 65396 (Placheta and Karobath, 1980), studies are underway that may delineate the precise role that C1-plays at the GABA-benzodiazepine-barbiturate-C1 --ionophore complex.…”

Section: Discussionmentioning

confidence: 98%

“…The role of C1-in regulating the components of the GABA receptor complex has been investigated in several laboratories. C 1~ has been implicated in the regulation of several GABA receptor components, namely, the benzodiazepine receptor , the barbiturate binding site (Asano and Ogasawara, 1981), the picrotoxin binding site (Fujimoto and Okabayashi, 1981), and the low-affinity GABA receptor (Matsumoto and Fukuda, 1983). Now, evidence has been obtained that suggests that the presence of C1-results in a modification of the high-affinity GABA receptor.…”

Section: Discussionmentioning

confidence: 99%

“…Also, the increased binding of GABA observed when barbituates bind to their recognition sites has been shown to be Cl--dependent (Asano and Ogasawara, 1981). Further, C1-has been observed to modify the actions of picrotoxin o n the ion gating process of the C1-ionophore (Fujimoto and Okabayashi, 1981;., 1982~). Finally, C1-has been demonstrated to increase the enhancing effect on GABA binding by two pyrazolopyridines with anxiolytic properties, SQ 20009 and SQ 65396 (Placheta and Karobath, 1980).…”

Section: Paul Madtes Jrmentioning

confidence: 99%

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Chloride Ions Preferentially Mask High‐Affinity GABA Binding Sites

Madtes

1984

Journal of Neurochemistry

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Chloride ions (Cl-) act to regulate the appearance of gamma-aminobutyric acid (GABA) binding sites in synaptic membranes from bovine retinas. Scatchard analysis indicates that the presence of Cl- results in a preferential decrease (85%) in the number of high-affinity binding sites, with no statistically significant change in the affinity (KD) of either the high- or low-affinity sites. The finding that the appearance of this binding site is altered by the presence of Cl- may indicate that Cl- acts, either directly or indirectly, to regulate the appearance, and hence function, of the high-affinity GABA receptor.

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Effect of picrotoxin on benzodiazepine receptors and GABA receptors with reference to the effect of Cl− ion

Cited by 31 publications

References 13 publications

A GABA‐activated chloride‐conductance not blocked by picrotoxin on spiny lobster neuromuscular preparations

A GABA‐activated chloride‐conductance not blocked by picrotoxin on spiny lobster neuromuscular preparations

gamma‐Aminobutyric acid hyperpolarizes rat hippocampal pyramidal cells through a calcium‐dependent potassium conductance.

Chloride Ions Preferentially Mask High‐Affinity GABA Binding Sites

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