Synthetic ω-conotoxin blocks synaptic transmission in the hippocampus in vitro

Kamiya, Haruyuki; Sawada, Satsuki; Yamamoto, Chosaburo

doi:10.1016/0304-3940(88)90253-4

Cited by 92 publications

(33 citation statements)

References 15 publications

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“…At central synapses, multiple calcium channel types, including N-type calcium channels, mediate the influx of calcium into presynaptic nerve terminals that is required for neurotransmitter release (Wu and Saggau, 1997). By depressing N-type calcium currents in presynaptic terminals, -CTX-G and -CTX-M inhibit both excitatory and inhibitory synaptic transmission (Kamiya et al, 1988;Dutar et al, 1989; Horne …”

Section: Discussionmentioning

confidence: 99%

“…In brain slice preparations, N-type calcium channel antagonists inhibit epileptiform activity (Boulton and O'Shaughnessy, 1991) by suppressing synaptic transmission (Kamiya et al, 1988;Dutar et al, 1989;Wu and Saggau, 1994). However, the toxins have limited bioavailability, and they distribute poorly in the brain so that they are not active systemically (Olivera et al, 1985;Miljanich and Ramachandran, 1995;Newcomb et al, 2000).…”

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confidence: 99%

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Prolonged Attenuation of Amygdala-Kindled Seizure Measures in Rats by Convection-Enhanced Delivery of the N-Type Calcium Channel Antagonists ω-Conotoxin GVIA and ω-Conotoxin MVIIA

Gąsior

White

Rogawski³

2007

J Pharmacol Exp Ther

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Convection-enhanced delivery (CED) permits the homogeneous distribution of therapeutic agents throughout localized regions of the brain parenchyma without causing tissue damage as occurs with bolus injection. Here, we examined whether CED infusion of the N-type calcium channel antagonists -conotoxin GVIA (-CTX-G) and -conotoxin MVIIA (-CTX-M) can attenuate kindling measures in fully amygdala-kindled rats. Rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received infusions of vehicle, -CTX-G (0.005, 0.05, and 0.5 nmol), -CTX-M (0.05, 0.15, and 0.5 nmol), proteolytically inactivated -CTX-M (0.5 nmol), or carbamazepine (500 nmol) into the stimulation site. CED of -CTX-G and -CTX-M over a 20-min period resulted in a dose-dependent increase in the afterdischarge threshold and a decrease in the afterdischarge duration and behavioral seizure score and duration during a period of 20 min to 1 week after the infusion, indicating an inhibitory effect on the triggering and expression of kindled seizures. The protective effects of -conotoxins reached a maximum at 48 h postinfusion, and then they gradually resolved over the next 5 days. In contrast, carbamazepine was active at 20 min but not at 24 h after the infusion, whereas CED of vehicle or inactivated -CTX-M had no effect. Except for transient tremor in some rats receiving the highest toxin doses, no adverse effects were observed. These results indicate that local CED of high-molecular-weight presynaptic N-type calcium channel blockers can produce long-lasting inhibition of brain excitability and that they may provide prolonged seizure protection in focal seizure disorders.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Prolonged Attenuation of Amygdala-Kindled Seizure Measures in Rats by Convection-Enhanced Delivery of the N-Type Calcium Channel Antagonists ω-Conotoxin GVIA and ω-Conotoxin MVIIA

Gąsior

White

Rogawski³

2007

J Pharmacol Exp Ther

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“…However, N-type VGCCs also had a detectable contribution in slices from more mature rats (Kamiya et al, 1988;Castillo et al, 1994;Tokunaga et al, 2004) so it is surprising that ethanol did not produce some inhibition of glutamate release in Figure 10. Glutamate release is regulated by the activity of N-and P/Q-type presynaptic VGCCs, and ethanol (EtOH) decreases transmitter release through inhibition of the N-type.…”

Section: Ethanol Affects Glutamatergic Synaptic Currents In Neonatal mentioning

confidence: 99%

Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission

Mameli¹,

Zamudio²,

Carta³

et al. 2005

J. Neurosci.

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Ethanol exposure during fetal development is a leading cause of learning disabilities. Studies suggest that it alters learning and memory by permanently damaging the hippocampus. It is generally assumed that this is mediated, in part, via alterations in glutamatergic transmission. Although NMDA receptors are presumed to be the most sensitive targets of ethanol in immature neurons, this issue has not been explored in the developing hippocampus. We performed whole-cell patch-clamp recordings in hippocampal slices from neonatal rats. Unexpectedly, we found that acute ethanol (10 -50 mM) exposure depresses inward currents elicited by local application of exogenous AMPA, but not NMDA, in CA3 pyramidal neurons. These findings revealed a direct effect of ethanol on postsynaptic AMPA receptors. Ethanol significantly decreased the amplitude of both AMPA and NMDA receptor-mediated EPSCs evoked by electrical stimulation. This effect was associated with an increase in the paired-pulse ratio and a decrease in the frequency of miniature EPSCs driven by depolarization of axonal terminals. These findings demonstrate that ethanol also acts at the presynaptic level. -Conotoxin-GVIA occluded the effect of ethanol on NMDA EPSCs, indicating that ethanol decreases glutamate release via inhibition of N-type voltage-gated Ca 2ϩ channels. In more mature rats, ethanol did not affect the probability of glutamate release or postsynaptic AMPA receptor-mediated currents, but it did inhibit NMDA-mediated currents. We conclude that the mechanism by which ethanol inhibits glutamatergic transmission is age dependent and challenge the view that postsynaptic NMDA receptors are the primary targets of ethanol early in development.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Turner

Adams

Dunlap

1993

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

232

122

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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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Synthetic ω-conotoxin blocks synaptic transmission in the hippocampus in vitro

Cited by 92 publications

References 15 publications

Prolonged Attenuation of Amygdala-Kindled Seizure Measures in Rats by Convection-Enhanced Delivery of the N-Type Calcium Channel Antagonists ω-Conotoxin GVIA and ω-Conotoxin MVIIA

Prolonged Attenuation of Amygdala-Kindled Seizure Measures in Rats by Convection-Enhanced Delivery of the N-Type Calcium Channel Antagonists ω-Conotoxin GVIA and ω-Conotoxin MVIIA

Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission

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

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