Lipid-soluble toxins thought to be specific for Na⁺ channels block Ca²⁺ channels in neuronal cells

Abstract

Many toxic compounds alter specifically the functioning of the fast sodium conductance that is responsible for the generation of action potentials in neuronal and muscle cells. One important class of these compounds consists of the lipid-soluble toxins, such as veratridine and other ceveratrum alkaloids, batrachotoxin, aconitine, and the diterpenoid grayanotoxins. These molecules are thought to bind to a common receptor site on the Na⁺ channel^1–5, thus inducing a membrane depolarization which can be suppressed by the addition of tetrodotoxin (TTX) or by the removal of Na⁺ from the incubation medium³. We show here that this family of molecules is not specific for the Na⁺ channel in neuroblastoma cells. Blockade of the voltage-dependent calcium channel is also observed, either in the toxin concentration range in which the molecules act on the Na⁺ channel (veratridine, grayanotoxin) or at even lower concentration (batrachotoxin).