Further Characterization of Phasic Calcium Influx in Rat Cerebrocortical Synaptosomes: Inferences Regarding Calcium Channel Type(s) in Nerve Endings

Suszkiw, Janusz B.; Murawsky, M.; Shi, Maggie M.

doi:10.1111/j.1471-4159.1989.tb01874.x

Cited by 101 publications

(30 citation statements)

References 35 publications

(40 reference statements)

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“…They are, however, consistent with previous studies on presynaptic nerve terminal Ca channels at many fast-transmitting synapses using more indirect techniques. These include insensitivity to DHP blockers (see Nachsen and Blaustein, 1979;Pemey et al, 1986;Miller, 1987;Himing et al, 1988;Suszkiw et al, 1989), slow inactivation (Suszkiw et al, 1986), and sensitivity to w-CTX (Kerr and Yoshikami, 1984;Yoshikami et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a calcium current in a vertebrate cholinergic presynaptic nerve terminal

1991

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Calcium currents were recorded from a cholinergic presynaptic nerve terminal in the chick ciliary ganglion using the whole-cell voltage- clamp technique. The presynaptic element of this synapse is in the form of a calyx that envelops the postsynaptic ciliary neuron. A method was developed to isolate the ciliary neuron, expose the calyx, and apply patch-clamp electrodes under visual control. The presynaptic Ca current activated at +30 mV with a fast time constant of about 1.5 msec and deactivated at -80 mV with a time constant of about 0.5 msec, values that are consistent with a role in action-potential-dependent transmitter release. The calyx Ca current was blocked by 0.1 mM Cd or 2 microM omega-conotoxin and was resistant to voltage-dependent inactivation. The presynaptic Ca channel exhibits similarities to the N- type group but differs from these by the minimal voltage-dependent inactivation. This type of channel, designated CaN-PT (N-like, presynaptic terminal), may play a key role in transmitter release at many vertebrate fast-transmitting synapses.

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Section: Discussionmentioning

confidence: 99%

Characterization of a calcium current in a vertebrate cholinergic presynaptic nerve terminal

1991

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“…Although presynaptic terminals possess high-affinity binding sites for dihydropyridine antagonists of L-type Ca2+ channels (Turner and Goldin, 1985;Suszkiw et al, 1986;Carvalho et al, 1986;Dunn, 1988;Massieu and Tapia, 1988) the consensus is that Ca" fluxes and transmitter release are insensitive to the inhibitors (Nachshen and Blaustein, 1979 ;Daniell and Leslie, 1983;Suszkiw et al, 1986Suszkiw et al, , 1989Reynolds et al, 1986;Carvalho et al, 1986;Massieu and Tapia, 1988) although a partial dihydropyridine sensitivity has also been reported for the initial rapid phase of 45Ca uptake (Turner and Goldin, 1985;Woodward et al, 1988a).…”

Section: Distinction Between Cytoplasmic and Vesicular Origins For Rementioning

confidence: 99%

The glutamatergic nerve terminal

Nicholls

1993

European Journal of Biochemistry

208

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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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“…One such antagonist, w-conotoxin GVIA (eoCgTx), was originally identified as an irreversible blocker of presynaptic release at the frog neuromuscular junction (5) and has been shown to specifically block N-type Ca2+ channels (6,7). Subsequent work showed that neurotransmitter release from peripheral neurons (8,9) and nerve terminal preparations (synaptosomes) from rat brain (10)(11)(12)(13)(14) was partially blocked by co-CgTx but not by 1,4-dihydropyridine antagonists that are specific for L channels. These results led to the widely accepted notion that neurosecretion is regulated primarily if not exclusively by N channels (15).…”

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Multiple Ca2+ channel types coexist to regulate synaptosomal neurotransmitter release.

Turner

Adams

Dunlap

1993

Proc. Natl. Acad. Sci. U.S.A.

232

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The regulation of excitation-secretion coupling by Ca2+ channels is a fundamental property of the nerve terminal. Peptide toxins that block specific Ca2+ channel types have been used to identify which channels participate in neurotransmitter release. Ca2+ channels in the nerve terminal regulate excitationsecretion coupling by controlling the entry of Ca2+ necessary for exocytosis (1). Multiple Ca2+ channel types in mammalian central neuron somata have been described (2-4), and several types can be defined based on their sensitivity to specific antagonists. One such antagonist, w-conotoxin GVIA (eoCgTx), was originally identified as an irreversible blocker of presynaptic release at the frog neuromuscular junction (5) and has been shown to specifically block N-type Ca2+ channels (6, 7). Subsequent work showed that neurotransmitter release from peripheral neurons (8, 9) and nerve terminal preparations (synaptosomes) from rat brain (10-14) was partially blocked by co-CgTx but not by 1,4-dihydropyridine antagonists that are specific for L channels. These results led to the widely accepted notion that neurosecretion is regulated primarily if not exclusively by N channels (15). co-CgTx can also block synaptic transmission in brain slice preparations (16)(17)(18), but the block is incomplete and in one case (18) was overcome by increased stimulus intensity. The partial block of neurotransmitter release as well as synaptic transmission suggested that o-CgTx-resistant channels may mediate excitation-secretion coupling at central synapses in some cases.More recently, co-CgTx-resistant Ca2+ channels have been described in mammalian brain. One such channel, the P type, was first characterized in Purkinje neurons, where it is the predominant Ca2+ channel (19). P channels, which have subsequently been found in many other regions, are specifThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.ically blocked by w-Aga-IVA, a peptide purified from the venom of Agelenopsis aperta (20). We demonstrated previously (21) that synaptosomal [3H]glutamate release was resistant to co-CgTx and partially but potently blocked by w-Aga-IVA, providing evidence for a role for P channels at glutamatergic synapses. We now report that [3H]dopamine release evoked by low levels of depolarization is partially blocked by w-CgTx as well as by w-Aga-IVA. However, under conditions of strong depolarization where neither toxin is very effective alone, a combination of nanomolar concentrations of both toxins is synergistic, producing substantial block of dopamine release. This.observation suggests that in striatum, P-type and N-type Ca2+ channels coexist and regulate secretion from dopaminergic nerve terminals, while P-type and a toxin-resistant Ca2+ channel type coexist to regulate glutamate release. This arrangement has significant implications for the regulation of excitation-secretion coupling...

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Further Characterization of Phasic Calcium Influx in Rat Cerebrocortical Synaptosomes: Inferences Regarding Calcium Channel Type(s) in Nerve Endings

Cited by 101 publications

References 35 publications

Characterization of a calcium current in a vertebrate cholinergic presynaptic nerve terminal

Characterization of a calcium current in a vertebrate cholinergic presynaptic nerve terminal

The glutamatergic nerve terminal

Multiple Ca2+ channel types coexist to regulate synaptosomal neurotransmitter release.

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