Binding of scorpion toxins to rat brain synaptosomal fraction. Effects of membrane potential, ions, and other neurotoxins

Jover, Emmanuel; Martin-Moutôt, Nicole; Couraud, François; Rochat, Hervé

doi:10.1021/bi00544a010

Cited by 86 publications

(75 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The binding of scorpion atoxins to receptor site 3 has been inhibited significantly by brevetoxin (Cestèle et al, 1995), a sodium-channel activator, foreseen to have a positive cooperativity. Likewise, TTX, which blocks the ion conductance through the pore by binding to receptor site 1 (Terlau et al, 1991), unexpectedly increases '-1.3-fold the binding of scorpion a-toxins to rat brain sodium channels (Ray et al, 1978;Jover et al, 1980;. In the present report, we propose an explanation for these observations.…”

supporting

confidence: 55%

“…As previously shown, saturable binding of ' 251-labeled scorpion atoxins is reduced '=90% between the resting membrane potential of synaptosomes at 5 mM K~[--55 mV (Blaustein and Goldring, 1975)] and the membrane potential at 135 mM K~[-~0 mV (Blaustein and Goldring, 1975)] ( Fig. 1A; Ray et al, 1978;Jover et al, 1980;Sharkey et al, 1987). The decrease in scorpion a-toxin binding with depolarization was shown to be due to a decrease in affinity, by increasing the dissociation rate constant (Catterall et al, 1976;Jover et al, 1980).…”

Section: Effect Of Depolarization On Veratridine Modulation Of Aah IImentioning

confidence: 57%

“…The concentration of the radiolabeled toxins was determined according to the specific activity of the 125j corresponding to 3,450-4,200 dpm/fmol of monoiodotoxin, depending on the time of use (the age of the iodine). (Blaustein and Goldring, 1975;Ray et al, 1978;Jover et al, 1980), the choline concentration was reduced so that [cholineI plus [K~] 251-AaH II. After incubation for 30 mm at 37°C,the reaction mixture was diluted with 2 ml of ice-cold wash buffer and filtered through GF/C filters under vacuum.…”

Section: Radioiodinationmentioning

confidence: 99%

“…The affinity of scorpion a-toxin binding to mammalian sodium channels was shown to decrease with membrane depolarization (Catterall, 1 977a,b, 1992;Ray et al, 1978;Jover et al, 1980). Depolarization induces a significant conformational change in the sodium-channel protein, indicated by gating charge movements, leading to activation of the channel (Sigworth, 1994).…”

mentioning

confidence: 99%

“…Consequently, we have used the high-affinity binding of a-toxin II from the venom of the scorpion Androctonus australis Hector (AaH II), the most active scorpion a-toxin in vertebrates (Gordon et a1., 1996), as a sensitive probe for subtle conformational changes in the receptor site 3 surface on rat brain sodium channels. We examined the effect of depolarization of synaptosomes by increasing K + concentration (Ray et al, 1978;Jover et al, 1980;Tamkun and Catterall, 1981;Sharkey et al, 1987) on the previously described allosteric modulation of scorpion a-toxin binding by veratridine, brevetoxin, and TTX. Many of the previous studies regularly used TTX in the binding medium of scorpion a-toxin, and scorpion a-toxin in the binding medium of [ 3H] batrachotoxinin A 20-abenzoate ([3H]BTX-B) (Ray et al, 1978;Catterall and Risk, 1981;Catterall and Gainer, 1985;Sharkey et al, 1987), complicating interpretation and possibly masking the effect of each toxin, as we have demonstrated recently .…”

mentioning

confidence: 99%

See 4 more Smart Citations

Depolarization Differentially Affects Allosteric Modulation by Neurotoxins of Scorpion α‐Toxin Binding on Voltage‐Gated Sodium Channels

Cestèle¹,

Gordon²

1998

Journal of Neurochemistry

View full text Add to dashboard Cite

Abstract:Voltage-gated sodium channels serve as a target for many neurotoxins that bind to several distinct, allosterically interacting receptor sites. We examined the effect of membrane potentials (incited by increasing external K~concentrations) on the binding modulation by veratridine, brevetoxin, and tetrodotoxin of the scorpion a-toxin AaH II to receptor site 3 on sodium channels of rat brain synaptosomes. Depolarization is shown to differentially modulate neurotoxin effects on AaH II binding: Veratridine increase is potentiated, brevetoxin's inhibitory effect is reduced, and tetrodotoxin enhancement is evident mainly at resting membrane potential (5 mM K~). Both tetrodotoxin and veratridine apparently reverse the inhibition of AaH II binding by brevetoxin at resting membrane potential, but only veratridine is able to partially restore AaH II binding at 0 mV (135 mM K~). Thus, the allosteric interactions are grouped into two categories, depending on the membrane potential. Under depolarized conditions, the cooperative effects among veratridine and brevetoxin on AaH II binding fit the previously described two-state conformational model. At resting membrane potential, additional interactions are revealed, which may be explained by assuming that toxin binding induces conformational changes on the channel structure, in addition to being state-dependent. Our results provide a new insight into neurotoxin action and the complex dynamic changes underlying allosteric coupling of neurotoxin receptor sites, which may be related to channel gating. Key Words: Allosteric interactionsNeurotoxins-Sodium channels-Scorpion a-toxinBrevetoxin.

show abstract

supporting

confidence: 55%

Section: Effect Of Depolarization On Veratridine Modulation Of Aah IImentioning

confidence: 57%

Section: Radioiodinationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Depolarization Differentially Affects Allosteric Modulation by Neurotoxins of Scorpion α‐Toxin Binding on Voltage‐Gated Sodium Channels

Cestèle¹,

Gordon²

1998

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

1H NMR structure of an antifungal γ-thionin protein SIα1: Similarity to scorpion toxins

et al. 1998

View full text Add to dashboard Cite

The three-dimensional structure of the Sorghum bicolor seed protein gamma-thionin SIalpha1 has been determined by 2D 1H nuclear magnetic resonance (NMR) spectroscopy. The secondary structure of this 47-residue antifungal protein with four disulphide bridges consists of a three-stranded antiparallel sheet and one helix. The helix is tethered to the sheet by two disulphide bridges which link two successive turns of the helix to alternate residues i, i+2 in one strand. Possible binding sites for antifungal activity are discussed. The same fold has been observed previously in several scorpion toxins.

show abstract

BmK AS: New scorpion neurotoxin binds to distinct receptor sites of mammal and insect voltage‐gated sodium channels

Liu

2000

J of Neuroscience Research

View full text Add to dashboard Cite

This study was undertaken to assess the binding properties of BmK AS on both mammal and insect excitable cell membranes. It was found that BmK AS bound specifically to a single class of non‐interacting binding sites on both rat brain and cockroach nerve cord synaptosomes with high affinity (Kd = 1.49 ± 0.14 and 0.79 ± 0.29 nM) and low capacity (Bmax = 1.39 ± 0.09 and 6.60 ± 1.25 pmol/mg protein), respectively. Binding kinetics showed that BmK AS could bind and reach equilibrium quickly, and dissociate partially from its binding sites on both kinds of synaptosomes. The binding of BmK AS was independent of membrane potential. Veratridine could not modify the binding of BmK AS. The competitive binding assay showed that specific binding of 125I‐BmK AS could be significantly inhibited by native BmK AS, BmK AS‐1, BmK IT2 and BmK IT on both synaptosomes. Unexpectedly, only about 20–30% binding of BmK AS on mammal synaptosomes was inhibited by BmK I at 10−5–10−9 M, but not on insect synaptosomes. It thus suggests that BmK AS type neurotoxins might bind to a distinct receptor site of sodium channels on mammal and insect excitable cell membranes with a manner similar to β‐scorpion toxins. J. Neurosci. Res. 61:541–548, 2000. © 2000 Wiley‐Liss, Inc.

show abstract

Binding of scorpion toxins to rat brain synaptosomal fraction. Effects of membrane potential, ions, and other neurotoxins

Cited by 86 publications

References 20 publications

Depolarization Differentially Affects Allosteric Modulation by Neurotoxins of Scorpion α‐Toxin Binding on Voltage‐Gated Sodium Channels

Depolarization Differentially Affects Allosteric Modulation by Neurotoxins of Scorpion α‐Toxin Binding on Voltage‐Gated Sodium Channels

1H NMR structure of an antifungal γ-thionin protein SIα1: Similarity to scorpion toxins

BmK AS: New scorpion neurotoxin binds to distinct receptor sites of mammal and insect voltage‐gated sodium channels

Contact Info

Product

Resources

About