Compared toxicity of the potassium channel blockers, apamin and dendrotoxin

Lallement, G.; Fosbraey, Paul; Baille-Le-Crom, V.; Tattersall, J.E.H.; Blanchet, Guy; Wetherell, Janet R.; Rice, Paul; Passingham, Sarah; Sentenac-Roumanou, H.

doi:10.1016/0300-483x(95)03120-5

Cited by 17 publications

(10 citation statements)

References 18 publications

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“…As previously described by Lallement et al (1995), DTx produces epileptiform bursting in hippocampal slices after a concentration-dependent delay. The bursts originate in the CA3 region and spread to CA1 and the dendate gyrus.…”

Section: Discussionmentioning

confidence: 85%

“…These are widely distributed throughout the central nervous system (CNS), particularly in the hippocampus (Halliwell et al, 1986;Pelchen-Matthews and Dolly, 1989;Sequier et al, 1990;Awan and Dolly, 1991;Nistri and Cherubini, 1992;Tsaur et al, 1992). After central injection, DTxs are able to induce limbic seizures originating from limbic or neocortical foci (Gandolfo et al, 1989a;Lallement et al, 1995). The neurochemical bases for the convulsive and neuropathological actions (Bagetta et al, 1992(Bagetta et al, , 1994Lallement et al, 1995) of DTxs are not completely understood, but these toxins are known to facilitate release of excitatory amino acids such as glutamate and other neurotransmitters (Docherty et al, 1983;Weller et al, 1985;Tibbs et al, 1989b;Barbeito et al, 1990;Hu et al, 1991;Ennis and Minchin, 1993).…”

Section: Introductionmentioning

confidence: 97%

“…Both a-DTx and 4-AP induce epileptiform bursting in hippocampal slices in vitro and increase the release of amino acid neurotransmitters from synaptosomes (Weller et al, 1985;Tibbs et al, 1989a;Barbeito et al, 1990;Perreault and Avoli, 1991;Lallement et al, 1995). The bursting induced by 4-AP can be blocked by non-Nmethyl-D-aspartate (NMDA) antagonists such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX), but not by NMDA antagonists such as D-2-amino-5-phosphonopentanoic acid (D-AP5) and (6) 3-3 (2-carboxypiperazine-4-yl) propyl-1-phosphonate (6CPP) (Perreault and Avoli, 1991), but similar studies have not been performed with a-DTx.…”

Section: Introductionmentioning

confidence: 99%

“…After central injection, DTxs are able to induce limbic seizures originating from limbic or neocortical foci (Gandolfo et al, 1989a;Lallement et al, 1995). The neurochemical bases for the convulsive and neuropathological actions (Bagetta et al, 1992(Bagetta et al, , 1994Lallement et al, 1995) of DTxs are not completely understood, but these toxins are known to facilitate release of excitatory amino acids such as glutamate and other neurotransmitters (Docherty et al, 1983;Weller et al, 1985;Tibbs et al, 1989b;Barbeito et al, 1990;Hu et al, 1991;Ennis and Minchin, 1993). Another blocker of these voltage-dependent potassium channels, 4-aminopyridine (4-AP), also has convulsive actions but does not cause the neuronal damage found with a-DTx (Bagetta et al, 1992(Bagetta et al, , 1994.…”

Section: Introductionmentioning

confidence: 99%

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Effects of excitatory amino acid antagonists on dendrotoxin-induced increases in neurotransmitter release and epileptiform bursting in rat hippocampus in vitro

et al. 1997

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Alpha-dendrotoxin (alpha-DTx), a snake venom toxin which blocks several types of fast-activating voltage-dependent potassium channels, induces limbic seizures and neuronal damage when injected into the brain. The mechanisms underlying these convulsant and neuropathological actions are not fully understood. We have studied the effects of alpha-DTx on neurotransmitter release and electrical activity in rat hippocampal brain slices and the role of excitatory amino acid receptors in mediating these actions of the toxin. alpha-DTx increased the basal release of acetylcholine, glutamate, aspartate, and GABA in a concentration-dependent manner and induced epileptiform bursting in the CA1 and CA3 regions of the slice. The increase in neurotransmitter release was evident during the first 4 min after toxin addition, whereas the bursting appeared after a concentration-dependent delay (20-40 min with 250 nM toxin). The N-methyl-D-aspartate (NMDA) receptor antagonists AP5 and MK-801 had no effect on the frequency or amplitude of dendrotoxin-induced epileptiform bursts, but the non-NMDA antagonists CNQX and DNQX abolished bursting in both CA1 and CA3 within 4-6 min. In contrast, the toxin-induced increases in neurotransmitter release were not blocked by DNQX. This study has demonstrated that, following exposure to alpha-DTx, there is a rapid increase in the release of neurotransmitters which precedes the onset of epileptiform bursting in the hippocampus. Since DNQX abolished the bursting but had no effect on the increase in neurotransmitter release, these results suggest that DNQX blocks alpha-DTx-induced epileptiform activity by antagonism of postsynaptic non-NMDA receptors.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of excitatory amino acid antagonists on dendrotoxin-induced increases in neurotransmitter release and epileptiform bursting in rat hippocampus in vitro

et al. 1997

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“…In fact, blockade of P-type Ca 2+ channels in wildtype PCs dramatically affects PC firing rates, as does direct blockade of the potassium channels (Womack and Khodakhah, 2002). Furthermore, the selective blockade of SK channels in vivo, through application of the channel antagonist apamin, promotes ataxia (Lallement et al, 1995). In support of this proposed mechanism for motor dysfunction in tottering, potassium channel blockers have been shown to inhibit stress-induced dystonia (Weisz et al, 2005).…”

Section: Consequences Of Postnatal Deficits In P-type Currentmentioning

confidence: 98%

Altered functional expression of Purkinje cell calcium channels precedes motor dysfunction in tottering mice

et al. 2007

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In tottering mice, a point mutation in the gene encoding P-type (Ca(v)2.1) voltage-gated calcium channels results in ataxia, absence epilepsy, and motor dystonia that appear 3-4 weeks postnatally. The aberrant motor behaviors have been linked to cerebellar dysfunction, and adult Purkinje cells (PCs) of tottering mice exhibit calcium-dependent changes in gene transcription suggestive of altered calcium homeostasis. In an attempt to identify early postnatal events important for the development of the behavioral phenotype, we examined calcium channel expression in cerebellar PCs from postnatal days 6-15 (P6-15). Whole cell recording was combined with selective calcium channel antagonists to allow discrimination of the various voltage-activated calcium channels types; early age-dependent differences between tottering and wild-type PCs were found. Wild-type PCs experienced a steady increase in P current density over this period, resulting in a twofold change by P15. In tottering, by contrast, P current density remained unchanged from P6-8 and was only 25% of the wild-type level by P8. A developmental delay in functional expression was implicated in this early deficit, since ensuing gains over the subsequent week brought tottering P current density close to the wild-type level by P15. At this age, tottering PCs also exhibited a 2.2-fold higher L-type calcium current density than that expressed by wild-type PCs. Increases in N current were apparent at some ages, most strikingly within a subset of tottering PCs at P15. Functional R- and T-type calcium current densities were equivalent to wild-type levels at all ages. We conclude that the tottering mutation brings about selective changes in functional calcium channel expression 1 to 2 weeks prior to the appearance of the behavioral deficits, raising the possibility that they represent an early, primary event along the path to motor dysfunction in tottering.

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Behavioral effects of a deletion in Kcnn2, the gene encoding the SK2 subunit of small-conductance Ca2+-activated K+ channels

et al. 2008

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Small-conductance Ca(2+)-activated potassium (SK) channels are heteromeric complexes of SK alpha-subunits and calmodulin that modulate membrane excitability, are responsible for part of the after-hyperpolarization (AHP) following action potentials, and thus control the firing patterns and excitability of most central neurons. An engineered knockout allele for the SK2 subunit has previously been reported. The hippocampal neurons of these mice lacked the medium latency component of the AHP, but the animals were not described as presenting any overt behavioral phenotype. In this report, we describe a deletion in the 5' region of the Kcnn2 gene encoding the SK2 subunit in the mouse neurological frissonnant (fri) mutant. The frissonnant mutant phenotype is characterized by constant rapid tremor and locomotor instability. It has been suggested, based merely on its phenotype, as a potential model for human Parkinson disease. We used a positional cloning strategy to identify the mutation underlying the frissonnant phenotype. We narrowed the genetic disease interval and identified a 3,441-bp deletion in the Kcnn2 gene, one of the three candidate genes present in the interval. Expression studies showed complete absence of normal Kcnn2 transcripts while some tissue-specific abnormal truncated variants were detected. Intracellular electrophysiological recordings of central vestibular neurons revealed permanent alterations of the AHP and firing behavior that might cause the tremor and associated locomotor deficits. Thus, the fri mutation suggests a new, potentially important physiological role, which had not been described, for the SK2 subunit of small-conductance Ca(2+)-activated potassium channels.

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Compared toxicity of the potassium channel blockers, apamin and dendrotoxin

Cited by 17 publications

References 18 publications

Effects of excitatory amino acid antagonists on dendrotoxin-induced increases in neurotransmitter release and epileptiform bursting in rat hippocampus in vitro

Effects of excitatory amino acid antagonists on dendrotoxin-induced increases in neurotransmitter release and epileptiform bursting in rat hippocampus in vitro

Altered functional expression of Purkinje cell calcium channels precedes motor dysfunction in tottering mice

Behavioral effects of a deletion in Kcnn2, the gene encoding the SK2 subunit of small-conductance Ca2+-activated K+ channels

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