Argiotoxin, a component of the spider venom from Argiope lobata, block
s AMPA receptor channels expressed in homomeric and heteromeric config
uration in Xenopus oocytes. Argiotoxin acts as an open channel blocker
in a voltage-dependent manner and discriminates between the functiona
lly diverse AMPA receptors. Importantly, a transmembrane region 2 dete
rminant for divalent cation permeability also determines argiotoxin se
nsitivity. Subunit-specific differences in the time courses of block a
nd recovery demonstrate that heteromeric AMPA receptors can assemble i
n variable ratios. Thus, argiotoxin can be used as a tool in analyzing
the subunit composition of AMPA receptors in native membranes.