rapid at an alkaline pH, which suggests that the unprotonated form may be more active. Neurotoxicity As a neurotoxin, it affects the nervous system. Neurological function depends on depolarization of nerve and muscle fibres due to increased sodium ion permeability of the excitable cell membrane. Lipid-soluble toxins such as batrachotoxin act directly on sodium ion channels involved in action potential generation and by modifying both their ion selectivity and voltage sensitivity. Batrachotoxin irreversibly binds to the Na+ channels which causes a conformational change in the channels that forces the sodium channels to remain open. Batrachotoxin not only keeps voltage-gated sodium channels open but also reduces single-channel conductance. In other words, the toxin binds to the sodium channel and keeps the membrane permeable to sodium ions in an "all or none" manner. This has a direct effect on the peripheral nervous system (PNS). Batrachotoxin in the PNS produces increased permeability (selective and irreversible) of the resting cell membrane to sodium ions, without changing potassium or calcium concentration. This influx of sodium depolarizes the formerly polarized cell membrane. Batrachotoxin also alters the ion selectivity of the ion channel by increasing the permeability of the channel toward larger cations. Voltage-sensitive sodium channels become persistently active at the resting membrane potential. Batrachotoxin kills by permanently blocking nerve signal transmission to the muscles. Batrachotoxin binds to and irreversibly opens the sodium channels of nerve cells and prevents them from closing. The neuron can no longer send signals and this results in paralysis. Furthermore, the massive influx of sodium ions produces osmotic alterations in nerves and muscles, which causes structural changes. It has been suggested that there may also be an effect on the central nervous system, although it is not currently known what such an effect may be. Cardiotoxicity Although generally classified as a neurotoxin, batrachotoxin has marked effects on heart muscles and its effects are mediated through sodium channel activation. Heart conduction is impaired resulting in arrhythmias, extrasystoles, ventricular fibrillation and other changes which lead to asystole and cardiac arrest. Batrachotoxin induces a massive release of acetylcholine in nerves and muscles and destruction of synaptic vesicles, as well. Batrachotoxin R is more toxic than related batrachotoxin A. Treatment Currently, no effective antidote exists for the treatment of batrachotoxin poisoning. Veratridine, aconitine and grayanotoxin—like batrachotoxin—are lipid-soluble poisons which similarly alter the ion selectivity of the sodium channels, suggesting a common site of action. Due to