Homologues of a K+ channel blocker α-dendrotoxin: characterization of synaptosomal binding sites and their coupling to elevation of cytosolic free calcium concentration

Muniz, Z.M.; Tibbs, Gareth R.; Maschot, P.; Bougis, Pierre E.; Nicholls, David G.; Dolly, J. Oliver

doi:10.1016/0197-0186(90)90130-l

Cited by 15 publications

(5 citation statements)

References 17 publications

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“…The finding (Fig. 1) that the Ba2+-evoked release of glutamate is sensitive to the Na+-channel inhibitor tetrodotoxin demonstrates that the cation acts on this preparation in a way similar to that of two other K+channel inhibitors, dendrotoxin (Tibbs et al, 1989a;Muniz et al, 1990) and 4-aminopyridine (Agoston et al, 1983;Tibbs et al, 1989b). In each case, the initial depolarization caused by the K+-channel blockade itself is inadequate to activate the Ca2+ channel coupled to release, but rather appears to "destabilize" the plasma membrane potential, allowing fluctuations in membrane potential to occur sufficient to fire repetitive action potentials.…”

Section: Bat+-evoked Spontaneous Action Potentials In Synaptosomesmentioning

confidence: 72%

“…1, trace c). Because Ba2+ inhibits K+ channels (Cook, 1988) and because we have reported previously that two K+-channel inhibitors, dendrotoxin (Tibbs et al, 1989~;Muniz et al, 1990) and 4-aminopyridine (Tibbs et al, 1989b) evoke the Ca2+-dependent release of glutamate from this preparation by apparently inducing spontaneous action potentials, we examined whether the Ba2+ response was blocked by the Na+-channel inhibitor tetrodotoxin, as are the responses in the presence of dendrotoxin and 4-aminopyridine. Trace e in Fig.…”

Section: Ba2+ Evokes a Tetrodotoxin-sensitive Glutamate Release In Thmentioning

confidence: 99%

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Barium‐Evoked Glutamate Release from Guinea‐Pig Cerebrocortical Synaptosomes

McMahon¹,

Nicholls²

1993

Journal of Neurochemistry

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Ba2+ has multiple effects on presynaptic terminals. The ion inhibits the K+ channels responsible for stabilizing the plasma membrane potential in the same way as previously reported for dendrotoxin and 4-aminopyridine. Secondly, the ion can substitute fully for Ca2+ in supporting KCl-evoked release of glutamate from guinea-pig cerebrocortical synaptosomes. In the latter case, the kinetics of glutamate release in the presence of saturating Ca2+ or Ba2+ are essentially identical. Substantially lower external concentrations of Ba2+ are required to achieve the same release kinetics as with Ca2+. The average internal free Ba2+ concentration attained during KCl depolarization is some 10-fold higher than that for Ca2+. However, because the fura-2 signal reflects predominantly the overflow of divalent cation after dissociation from the release trigger, it is not the valid parameter to compare effectiveness of the cations in triggering glutamate exocytosis. In view of the established inability of Ba2+ to interact with calmodulin, these results are discussed in relation to theories in which Ca2+/calmodulin-dependent protein kinase-mediated phosphorylation is a prerequisite for synaptic vesicle exocytosis.

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Section: Bat+-evoked Spontaneous Action Potentials In Synaptosomesmentioning

confidence: 72%

Section: Ba2+ Evokes a Tetrodotoxin-sensitive Glutamate Release In Thmentioning

confidence: 99%

Barium‐Evoked Glutamate Release from Guinea‐Pig Cerebrocortical Synaptosomes

McMahon¹,

Nicholls²

1993

Journal of Neurochemistry

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“…Thus inhibition of the channel by the addition to synaptosomes of either nanomolar dendrotoxin or millimolar 4aminopyridine (4AP) abolishes this negative feedback and causes synaptosomes to undergo spontaneous 'epileptic' action potentials (Fig. 3), involving the repetitive firing of Na' channels, as though the terminal was still receiving action potentials down its severed axon (Agoston et al 1983;Tibbs et al, 1989a,b,c;Muniz et al, 1990). 4AP thus more closely mimics the physiological mechanism of terminal depolarization than does elevated KCl.…”

Section: Depolarization By Potassium Channel Inhibitionmentioning

confidence: 99%

The glutamatergic nerve terminal

Nicholls

1994

EJB Reviews 1993

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Glutamate as a neurotransmitterThe human brain has about lolo neurones, each of which, on average, makes about 1000 synaptic contacts with other neurones. Of these l O I 3 synapses perhaps up to 90% utilize amino acids as their neurotransmitter. Glutamate is the major excitatory amino acid (acting predominantly on depolarizing post-synaptic receptors) while 4-aminobutyrate (GABA) and glycine are the major inhibitory transmitters (acting on hyper-polarizing receptors). As well as playing the dominant role in fast information transfer, glutamate is of particular interest in view of its involvement in current models of memory and learning (Bliss and Dolphin, 1982;Cotman et al., 1988;Collingridge and Singer, 1990) and because a pathological release of glutamate in brain ischaemia is neurotoxic and a major contributor to the damage caused under these conditions (Rothman and Olney, 1986;Choi, 1988 ;Meldrum and Garthwaite, 1990).A synapse has a pre-synaptic element responsible for the storage and release of transmitter and a post-synaptic element containing one or more classes of receptor for the transmitter. The potent combination of electrophysiology and molecular cloning has allowed a dramatic advance in our understanding of post-synaptic events. Three classes of post-synaptic ionotropic (possessing an integral ion channel) glutamate receptors have been identified and cloned: the 2-amino-3hydroxy-5-methyl-4-isoxazole propionatekainate (AMPA/ KA) receptor Nakanishi et al., 1990;Sakmann, 1992), the high-affinity KA receptor (Egebjerg et al., 1991) and the N-methyl D-aSpartate (NMDA) receptor (Moriyoshi et al., 1991 ;Kumar et al., 1991 ;Barnard, 1992). Each can exist in many isoforms by combining subunits formed from distinct genes, by alternative splicing or by post-transcriptional modification (Monyer et al., 1991 ;Burnashev et al., 1992).The AMPNKA receptor is responsible for fast information transfer while the NMDA receptor is only operative when the post-synaptic membrane is independently depolarized by another receptor. This 'associative' behaviour of the latter is believed to underlie aspects of the learning process.

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“…Thus inhibition of the channel by the addition to synaptosomes of either nanomolar dendrotoxin or millimolar 4-aminopyridine (4AP) abolishes this negative feedback and causes synaptosomes to undergo spontaneous 'epileptic' action potentials (Fig. 3), involving the repetitive firing of Na' channels, as though the terminal was still receiving action potentials down its severed axon (Agoston et al 1983;Tibbs et al, 1989a,b,c;Muniz et al, 1990). 4AP thus more closely mimics the physiological mechanism of terminal depolarization than does elevated KCl.…”

Section: Depolarization By Potassium Channel Inhibitionmentioning

confidence: 99%

The glutamatergic nerve terminal

Nicholls

1993

European Journal of Biochemistry

207

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Glutamate as a neurotransmitterThe human brain has about lolo neurones, each of which, on average, makes about 1000 synaptic contacts with other neurones. Of these l O I 3 synapses perhaps up to 90% utilize amino acids as their neurotransmitter. Glutamate is the major excitatory amino acid (acting predominantly on depolarizing post-synaptic receptors) while 4-aminobutyrate (GABA) and glycine are the major inhibitory transmitters (acting on hyper-polarizing receptors). As well as playing the dominant role in fast information transfer, glutamate is of particular interest in view of its involvement in current models of memory and learning (Bliss and Dolphin, 1982;Cotman et al., 1988;Collingridge and Singer, 1990) and because a pathological release of glutamate in brain ischaemia is neurotoxic and a major contributor to the damage caused under these conditions (Rothman and Olney, 1986;Choi, 1988 ;Meldrum and Garthwaite, 1990).A synapse has a pre-synaptic element responsible for the storage and release of transmitter and a post-synaptic element containing one or more classes of receptor for the transmitter. The potent combination of electrophysiology and molecular cloning has allowed a dramatic advance in our understanding of post-synaptic events. Three classes of post-synaptic ionotropic (possessing an integral ion channel) glutamate receptors have been identified and cloned: the 2-amino-3-hydroxy-5-methyl-4-isoxazole propionatekainate (AMPA/ KA) receptor Nakanishi et al., 1990;Sakmann, 1992), the high-affinity KA receptor (Egebjerg et al., 1991) and the N-methyl D-aSpartate (NMDA) receptor (Moriyoshi et al., 1991 ; Kumar et al., 1991 ;Barnard, 1992). Each can exist in many isoforms by combining subunits formed from distinct genes, by alternative splicing or by post-transcriptional modification (Monyer et al., 1991 ;Burnashev et al., 1992).The AMPNKA receptor is responsible for fast information transfer while the NMDA receptor is only operative when the post-synaptic membrane is independently depolarized by another receptor. This 'associative' behaviour of the latter is believed to underlie aspects of the learning process.

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Homologues of a K+ channel blocker α-dendrotoxin: characterization of synaptosomal binding sites and their coupling to elevation of cytosolic free calcium concentration

Cited by 15 publications

References 17 publications

Barium‐Evoked Glutamate Release from Guinea‐Pig Cerebrocortical Synaptosomes

Barium‐Evoked Glutamate Release from Guinea‐Pig Cerebrocortical Synaptosomes

The glutamatergic nerve terminal

The glutamatergic nerve terminal

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