Dendrotoxin and charybdotoxin increase the cytosolic concentration of free Ca<sup>2+</sup> in cerebrocortical synaptosomes: An effect not shared by apamin

Tibbs, Gareth R.; Nicholls, David G.; Dolly, J. Oliver

doi:10.1016/0014-5793(89)81081-6

Cited by 19 publications

(5 citation statements)

References 24 publications

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“…Of the known Shaker-like K+ channels, Kv 1.2 is particularly sensitive to 4AP and DTX (Stiihmer et al, 1989). Although these pharmacological features are not necessarily unique to Kv 1.2-containing K+ channels in vivo, it is, nevertheless, worth noting that DTX-sensitive and 4AP-sensitive K+ currents have been described that are consistent with immunolocalization of Kv1.2 reported here, for example, in the somatodendritic domain of hippocampal pyramidal neurons (Halliwell et al, 1986) in nerve terminals (Anderson and Harvey, 1988;Dolly, 1988;Tibbs et al, 1989;Bielefeldt et al, 1992), and in myelinated nerve fibers (Dubois, 1983;Benoit and Dubois, 1986). Participation of Kv 1.2 in these channels could account for their similar pharmacology, while the differences in kinetic behavior of these conductances could be explained by Kv 1.2 coassembly with different K+ channel subunits in these various locations.…”

Section: Functional Implications Of Kv12 Localizationsupporting

confidence: 82%

Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain

et al. 1994

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In the nervous system, a wide diversity of K+ channels are formed by the oligomeric assembly of subunits encoded by a large number of K+ channel genes. The physiological functions of a specific K+ channel subunit in vivo will be dictated in part by its subcellular location within neurons. We have used a combined in situ hybridization and immunocytochemical approach to determine the subcellular distribution of Kv1.2, a member of the Shaker subfamily of K+ channel genes. In contrast to other characterized K+ channel subunits, Kv1.2 protein shows a complex differential subcellular distribution in neurons of rat brain. In some of these neurons (e.g., hippocampal and cortical pyramidal cells, and Purkinje cells), Kv1.2 is concentrated in dendrites, while in others (e.g., cerebellar basket cells), Kv 1.2 is predominantly, if not exclusively, localized to nerve terminals. Furthermore, Kv1.2 immunoreactivity was also detected in certain axon tracts. We hypothesize that the differential sorting of Kv1.2 could result from association of Kv1.2 with varying heterologous K+ channel subunits in different cell types, with the implication that Kv1.2 may participate in distinct heteromultimeric K+ channels in different subcellular domains. The findings suggest that Kv1.2-containing K+ channels may play diverse functional roles in several neuronal compartments, regulating presynaptic or postsynaptic membrane excitability, depending on the neuronal cell type.

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Section: Functional Implications Of Kv12 Localizationsupporting

confidence: 82%

Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain

et al. 1994

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“…However, 100 pM toxin did not show any significant inhibition of ATP synthesis in thylakoid membranes. This indicates that a-dendrotoxin and charybdotoxin apparently recognize similiar target sites on CFoCFl which can not be recognized by apamin Similar results for the three toxins have been obtained previously [42].…”

Section: Fractionation Of Crude Lq Venomsupporting

confidence: 74%

Inhibition of chloroplast ATPase by the K⁺ channel blocker α‐dendrotoxin

Schulenburg

Schwarz

Wagner

1992

European Journal of Biochemistry

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Possible structural and functional similarities between the channel part, CFo, of chloroplast ATPase (CFoCFl) and ion channels permeable to monovalent cations were investigated using highaffinity toxins mainly targeted against voltage-sensitive K + channels. In particular, the effect of the K+-channel blocker a-dendrotoxin and the crude scorpion venom of Leiurus quinquestriutus hebraeus (LQ venom) on ATP synthesis in thylakoid membranes and in CFoCFl-containing liposomes was characterised.a-dendrotoxin (Ki z 5.05 pM) and the LQ venom (Ki z 1.55 pg/ml) specifically inhibited ATP synthesis in thylakoid membranes and in CFoCF1-containing liposomes. Our results show that adendrotoxin and peptides of the LQ venom with an apparent molecular mass of about 4.0 kDa, probably isoforms of charybdotoxin, specifically bind to CFoCFl. This binding was reversible and induced a high leak conductance for H + through CFo. The Ca2+-dependent ATPase activity of the isolated soluble part of CFoCF1 (CF,) was completely inhibited by 1 pM a-dendrotoxin, while the crude LQ venom, at concentrations up to 10 Fg/ml, had no affect on ATPase activity. The concentration dependence of the inhibition by a-dendrotoxin indicates that approximately 2 mol adendrotoxin bind/mol CFoCFl and 1 mol a-dendrotoxin/mol CF1. Known inhibitors of H+-flowthrough CFo acted in the presence of a-dendrotoxin synergistically. Dicyclohexylcarbodiimide and venturicidin, in contrast to their known effect of blocking H+-flow-through CFo, increased the leak conductance through CFo in the presence of a-dendrotoxin drastically. This uncoupling effect indicates that their normal mode of blocking is a secondary effect. Binding of the inhibitors to their respective sites apparently does not affect the proton pathway in CFo, but induces a conformation which closes the channel part for H + . channel. According to secondary-structure predictions, the homologous sequences in subunit 111 and the shaker K + channel represent putative hydrophilic loops connecting two transmembrane a-helices. Apparently the shaker K + channel and subunit I11 share significant topological features in these hydrophilic loops which may be part of the respective channel entrance.The key enzymes of energy conversion in the membrane of bacteria, mitochondria and chloroplasts, the H+-translocating F-type ATPases, are composed of two moieties: the water-soluble part F,, containing the catalytic sites, and the intrinsic membrane part, Fo, involved in H + translocation

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“…These data indicate that 4-AP at 1 mM inhibits both a-Dtx-sensitive and cr-Dtx-insensitive channels. In contrast, Ctx addition after either a-Dtx (Tibbs et a!., 1989c) or 4-AP ( Fig. 3B) results in a further small rise in [Ca2~]~(28 ±5%, n = 3 and 19 ± 1%, n = 4, respectively).…”

Section: Resultsmentioning

confidence: 90%

Evidence for the Induction of Repetitive Action Potentials in Synaptosomes by K⁺‐Channel Inhibitors: An Analysis of Plasma Membrane Ion Fluxes

Tibbs

Dolly

Nicholls

1996

Journal of Neurochemistry

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The effects of four K~-channelinhibitors on synaptosomal free Ca 2~concentrations and 86Rbfluxes are analysed. 4-Aminopyridine, a-dendrotoxin, charybdotoxin, and tetraethylammonium all increase the free Ca2~concentration, although their potencies differ widely. In each case, the elevation in free Ca2concentration is reversed by the subsequent addition of tetrodotoxin. The transient SSRbr efflux from preequilibrated synaptosomes induced with high concentrations of veratridine is partially inhibited by 4-aminopyridine and a-dendrotoxin. In contrast, when 4-aminopyridine or a-dendrotoxin is added to polarized synaptosomes, an enhanced 86Rb~flux is seen, both for uptake and for efflux with no change in the total 86Rb~/Kcontent of the synaptosomes and with only a slight time-averaged plasma membrane depolarization (6.4 and 3.3 mV, respectively). The enhancements of flux by 4-aminopyridine or a-dendrotoxin are sensitive to ouabain and/or to tetrodotoxin. Furthermore, these flux changes show the same concentration dependencies as the blocked component of veratridine-stimulated 86Rb~efflux, the elevation of free Ca2c oncentration, and the facilitation of glutamate exocytosis that are elicited by 4-aminopyridine or a-dendrotoxin. It is concluded that these findings support the proposal of spontaneous, repetitive firing of synaptosomes evoked by K~-channel inhibitors and that the enhanced 86Rb + flux isa consequence of the activity of 4-aminopyridine-and et-dendrotoxin--insensitive Kchannels during these action potentials.

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Dendrotoxin and charybdotoxin increase the cytosolic concentration of free Ca²⁺ in cerebrocortical synaptosomes: An effect not shared by apamin

Cited by 19 publications

References 24 publications

Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain

Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain

Inhibition of chloroplast ATPase by the K⁺ channel blocker α‐dendrotoxin

Evidence for the Induction of Repetitive Action Potentials in Synaptosomes by K⁺‐Channel Inhibitors: An Analysis of Plasma Membrane Ion Fluxes

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Dendrotoxin and charybdotoxin increase the cytosolic concentration of free Ca2+ in cerebrocortical synaptosomes: An effect not shared by apamin

Cited by 19 publications

References 24 publications

Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain

Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain

Inhibition of chloroplast ATPase by the K+ channel blocker α‐dendrotoxin

Evidence for the Induction of Repetitive Action Potentials in Synaptosomes by K+‐Channel Inhibitors: An Analysis of Plasma Membrane Ion Fluxes

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Dendrotoxin and charybdotoxin increase the cytosolic concentration of free Ca²⁺ in cerebrocortical synaptosomes: An effect not shared by apamin

Inhibition of chloroplast ATPase by the K⁺ channel blocker α‐dendrotoxin

Evidence for the Induction of Repetitive Action Potentials in Synaptosomes by K⁺‐Channel Inhibitors: An Analysis of Plasma Membrane Ion Fluxes