Channels produced by spider venoms in bilayer lipid membrane: mechanisms of ion transport and toxic action

Abstract

The selectivity of ion channels produced by latrotoxin obtained from a black widow spider venom and by venom from the spider Steatoda paykulliana in bilayer phospholipid membrane was studied. Experimental current-voltage curves of these channels were used for the estimation of parameters of a two barrier model of their energy profiles. Selectivities of both types of channels are similar. Alkaline earth cations are permeable, the permeability increasing in the order Mg2+ less than Ca2+ less than Sr2+ less than Ba2+. In contrast transition metal cations block the channel, their efficiency decreases in the order: Cd2+ greater than or equal to Ni2+ greater than Zn2+ greater than Co2+ greater than Mn2+ (Steatoda paykulliana spider venom) and Cd2+ greater than Co2+ greater than Ni2+ greater than Zn2+ greater than Mn2+ (latrotoxin). Amplitudes of current carried by corresponding ions are mainly determined by the depth of the potential well for this ion, i.e., by its affinity to the cation binding site in the channel. The channels are also permeable to monovalent cations but they do not bind them. Selectivity for monovalent cations depends on Ca2+ concentration at the cis-side of membrane in the micromolar range. However, the addition of Ca2+ to the trans-side up to 10 mM does not affect currents carried by monovalent ions. It is suggested that venom-induced calcium channels have two conformational states with different selectivities which interconvert upon binding one calcium ion. Possible general schemes for the organisation of calcium channels in excitable membranes are also discussed. Finally, using a mathematical model of synaptic transmission, possible mechanisms of toxic action of spider venoms are considered.