Molecular aspects of neuronal voltage‐dependent K<sup>+</sup> channels

Rehm, Hubert

doi:10.1111/j.1432-1033.1991.tb16425.x

Cited by 33 publications

(17 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Expression of DTx was previously described in a preliminary report abstract of the Xth Meeting on Toxinology which was held in Paris on 2-4 September 1992. has been shown recently that the DTx binding site on rat brain potassium channel is located in an extracellular domain which includes an essential negatively charged residue ([ 17,181, for review see [19]). …”

Section: Introductionmentioning

confidence: 99%

On the site by which α‐dendrotoxin binds to voltage‐dependent potassium channels: Site‐directed mutagenesis reveals that the lysine triplet 28–30 is not essential for binding

Danse¹,

Rowan²,

Gasparini³

et al. 1994

FEBS Letters

View full text Add to dashboard Cite

We constructed a synthetic gene encoding the published amino acid sequence of DTx from Dendroaspis angusticeps, a ligand of voltagedependent postassium channels that facilitates neurotransmitter release. We expressed it in Escherichia coli as a fusion protein secreted in the culture medium. The recombinant DTx was generated in vitro by chemical treatment and recovered as two isoforms. One of them (rDTx), like the venom toxin, has an N-terminal pyroglutamate whereas the other (rQDTx) has a free N-terminal glutamine. Chromatographic differences between rDTx and natural DTx led us to re-examine the amino acid sequence of natural DTx. In contrast to what was previously published, position 12 was an Asp and not Asn. Despite this difference, rDTx and DTx had similar toxicity in mice and binding affinity to synaptosomes, suggesting that residue 12 is not important for DTx function. Nor is the N-terminal residue implicated in DTx function since rDTx and QDTx also had similar biological activities. We also synthesized and expressed a mutant of the DTx gene in which the lysine triplet 28-30 was changed into Ala-Ala-Gly. The two resulting recombinant isoforms exhibited only small decreases in biological activity, excluding the possibility that the positively charged lysine triplet 28-30 of DTx is directly involved in the toxin functional site.

show abstract

Section: Introductionmentioning

confidence: 99%

On the site by which α‐dendrotoxin binds to voltage‐dependent potassium channels: Site‐directed mutagenesis reveals that the lysine triplet 28–30 is not essential for binding

Danse¹,

Rowan²,

Gasparini³

et al. 1994

FEBS Letters

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

“…Surprisingly, only a relatively small number of toxins active on these channels has yet been discovered (3, 4). They are MCD peptide from bee venom (5, 6), charybdotoxin and analogs from different scorpion species (7-14), ␤-bungarotoxin (15, 16), and dendrotoxins from mamba venoms (3,5,(17)(18)(19)(20)(21)(22).These different toxins only block the expression of four of the cloned Kv channels (Kv1.1, Kv1.2, and Kv1.6 for MCD peptide and dendrotoxin, Kv1.1, Kv1.2, Kv1.3, and Kv1.6 for charybdotoxin) (reviewed in Ref. 23).…”

mentioning

confidence: 99%

Kalicludines and Kaliseptine

Schweitz

Bruhn

Guillemare

et al. 1995

Journal of Biological Chemistry

204

140

View full text Add to dashboard Cite

Potassium channels have an essential role in repolarization phases of action potentials and in the fine regulation of the resting potential. Molecular cloning has recently led to the identification of a large number (over 15) of genes for voltagesensitive, non inward-rectifier, K ϩ (Kv) channels (1, 2) which, when expressed in Xenopus oocytes, generate a variety of K ϩ channel activities with different kinetics, voltage dependences, conductances, and regulation properties. Surprisingly, only a relatively small number of toxins active on these channels has yet been discovered (3, 4). They are MCD peptide from bee venom (5, 6), charybdotoxin and analogs from different scorpion species (7-14), ␤-bungarotoxin (15, 16), and dendrotoxins from mamba venoms (3,5,(17)(18)(19)(20)(21)(22).These different toxins only block the expression of four of the cloned Kv channels (Kv1.1, Kv1.2, and Kv1.6 for MCD peptide and dendrotoxin, Kv1.1, Kv1.2, Kv1.3, and Kv1.6 for charybdotoxin) (reviewed in Ref. 23). Binding studies using radioiodinated derivatives of these toxins have been essential for the identification, purification, and determination of the subunit structure (6, 24 -26) of these Kv channels. These toxins have also been important for the first brain localizations of Kv channels (16,27) and are particularly interesting inducers of long term potentiation (28).Sea anemones produce toxins with which they paralyze their prey. They are particularly important as sources of toxins active on voltage-dependent Na ϩ channel which have been essential tools for studying the structure, the mechanism, and the diversity of this channel type (29 -38).This paper reports the isolation, structure, and properties of a series of new toxins from Anemonia sulcata which behave as blockers of Kv channels. EXPERIMENTAL PROCEDURES Materials-Trypsin, the Kunitz trypsin inhibitor (BPTI),1 and N ␣ -benzoyl-DL-arginine p-nitroanilide (BAPNA) were obtained from Sigma. Sephadex G-25, Sephadex G-50, SP Sephadex C-25 were obtained from Pharmacia, Fractogel TSK HW-50 (F), Fractogel EMD SO 3 -650 (M), and RP18 Lichrocart were from Merck. For HPLC columns, TSK SP 5PW was from Toyosoda. Ultrasphere ODS was from Beckman, Hypersil BDS was from SFCC Shandon, and Alltima was from Alltech. HPLC purifications were performed with a Waters system.Purification of Anemonia Sulcata Peptides-The first steps of this purification were performed with slight modifications of a method previously described for the isolation of Na ϩ channel toxins of A. sulcata (39). In this procedure 12 g of the crude sea anemone toxin (Ref. 39; Fig. 2B1) was dissolved in 120 ml of NaCl 1 M and regelfiltered in two parts on a Sephadex G-50 medium column (7 ϫ 140 cm) equilibrated in 1 M NaCl. The crab paralyzing fractions of these gel filtrations were combined, dialyzed in a Visking Dialysis tube (molecular weight cutoff 12,000 -14,000) for 5 h, concentrated at reduced pressure, and desalted on a Sephadex G-25 column (7 ϫ 70 cm) equilibrated with 0.3 M acetic acid. After a concentration at red...

show abstract

“…Besides β -bungarotoxin [32, 33], early studies with the neurotoxic sPLA 2 OS2 from Australian Taipan snake Oxyuranus scutellatus scutellatus have led to the identification of two families of binding proteins called N- and M-type receptors [31, 34, 35]. The N-type receptors are present in mammalian brain and other tissues.…”

Section: Viperidae Snake Venom Phospholipase A2 Enzymes: Secreted mentioning

confidence: 99%

Antitumoral Potential of Tunisian Snake Venoms Secreted Phospholipases A₂

Zouari-Kessentini

Srairi-Abid

Bazaa

et al. 2013

BioMed Research International

View full text Add to dashboard Cite

Phospholipases type A2 (PLA2s) are the most abundant proteins found in Viperidae snake venom. They are quite fascinating from both a biological and structural point of view. Despite similarity in their structures and common catalytic properties, they exhibit a wide spectrum of pharmacological activities. Besides being hydrolases, secreted phospholipases A2 (sPLA2) are an important group of toxins, whose action at the molecular level is still a matter of debate. These proteins can display toxic effects by different mechanisms. In addition to neurotoxicity, myotoxicity, hemolytic activity, antibacterial, anticoagulant, and antiplatelet effects, some venom PLA2s show antitumor and antiangiogenic activities by mechanisms independent of their enzymatic activity. This paper aims to discuss original finding against anti-tumor and anti-angiogenic activities of sPLA2 isolated from Tunisian vipers: Cerastes cerastes and Macrovipera lebetina, representing new tools to target specific integrins, mainly, α5β1 and αv integrins.

show abstract

Molecular aspects of neuronal voltage‐dependent K⁺ channels

Cited by 33 publications

References 137 publications

On the site by which α‐dendrotoxin binds to voltage‐dependent potassium channels: Site‐directed mutagenesis reveals that the lysine triplet 28–30 is not essential for binding

On the site by which α‐dendrotoxin binds to voltage‐dependent potassium channels: Site‐directed mutagenesis reveals that the lysine triplet 28–30 is not essential for binding

Kalicludines and Kaliseptine

Antitumoral Potential of Tunisian Snake Venoms Secreted Phospholipases A₂

Contact Info

Product

Resources

About

Molecular aspects of neuronal voltage‐dependent K+ channels

Cited by 33 publications

References 137 publications

On the site by which α‐dendrotoxin binds to voltage‐dependent potassium channels: Site‐directed mutagenesis reveals that the lysine triplet 28–30 is not essential for binding

On the site by which α‐dendrotoxin binds to voltage‐dependent potassium channels: Site‐directed mutagenesis reveals that the lysine triplet 28–30 is not essential for binding

Kalicludines and Kaliseptine

Antitumoral Potential of Tunisian Snake Venoms Secreted Phospholipases A2

Contact Info

Product

Resources

About

Molecular aspects of neuronal voltage‐dependent K⁺ channels

Antitumoral Potential of Tunisian Snake Venoms Secreted Phospholipases A₂