Batrachotoxin binding

Batrachotoxins bind specifically to voltage-gated sodium channels in nerve and muscle membranes. 

Brevetoxins which bind to site 5, enhance the veratridine-activated Na+ influx in neuroblastoma cells (Catterall and Risk 1981) they increase Poo rather than reduce Ko.s (Catterall and Gainer 1985). However in vera-tridine-treated adrenal medullary cells the brevetoxin PbTx-3 increases both Poo and affinity, again determined by Na+ influx measurements (Wada et al. 1994). Brevetoxins also enhance batrachotoxin binding, and this effect is very much potentiated by certain pyrethroids, for example. 

RU 39568, which alone increases binding about 400-fold addition of a high concentration of veratridine (300 (iM) reduces batrachotoxin binding to 1%, demonstrating the specific allosteric effect of this pyrethroid (Trainer et al. 1993 see also Sect. 8). Another site-5 neurotoxin, ciguatoxin, enhances Na+ uptake in neuroblastoma cells and myoblasts in synergy with veratridine at even lower concentration (Bidard et al. 1984). A common feature of these site-5 toxins is that, by themselves, they do not increase fluxes. 

The effect of batrachotoxin on sodium fluxes has been studied extensively in neuroblastoma cells (see Table 5 at the end of this section for references). This system has been invaluable for delineating interactions of batrachotoxin with polypeptides. Such interactions involve allosteric modifications of the voltage-dependent sodium channel 57,59). It has been proposed that batrachotoxin binds selectively to an active state of the channel and that partial agonists such as aconitine and veratridine bind to both active and inactive states 168). Polypeptides such as scorpion toxin have been proposed to inhibit the conversion of active to inactive state, thereby decreasing the amount of inactive state available to the alkaloids. 

Batrachotoxinin-A 20a-p-pH] benzoate (pH]-BTX-B) has proven to be a satisfactory ligand for the investigation of batrachotoxin-binding sites in brain membranes and synaptosomes (45,46,66). The affinity constant for [3H]-BTX-B is approximately 50 nM in the presence of scorpion toxin and approximately 700 nM in the absence of a polypeptide. The density of sites... 

A growing number of other diverse compounds have also been shown to bind to an allosteric site on the muscarinic receptors. Among them are pirenzepine (highly selective for Mi receptor), lidocaine and verapamil (ion channel blockers), tacrine (anticholinesterase compound), batrachotoxin, and strychnine (glycine receptor antagonist) [25,31-35],... 

IV) ANTIARRHYTHMIC. It is a SMOOTH MUSCLE RELAXANT and coronary VASODILATOR. It can be used as an antihypertensive and antianginal. and in antimigraine prophylaxis, verapamil hydrochloride verapamil, veratridine is an alkaloid from Schoenocaulon officinale (Liliaceae), and is a neurotoxin and sodium-Channel ACTIVATOR that binds to Na -channels, leading to depolarization. It has similar but weaker actions to batrachotoxin. Vercyte pipobroman. 

The interaction of (+)-kavain with receptor site 1 of Na channels, which is the epitope of antagonists like saxitoxin and tetrodotoxin, and its influence on site 2, the binding site of agonists including veratridine, batrachotoxin, and aconitine, were investigated on cerebrocortical synaptosomes by radioligand-binding assays. 

Ciguatoxin (exotic fish, Moray eel) and batrachotoxin (South American frogs) bind in the Na+ channel, keeping it open to cause a persistent depolarization and channel inactivation. 

Ibogaine inhibited (Ki 8.1 yu.M) [3H]batrachotoxin A 20-a-benzoate binding to voltage-dependent sodium channels in depolarized mouse neu-... 

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