Allosteric modification of α-bungarotoxin binding by the ‘calcium channel antagonist’ verapamil
Abstract The putative calcium channel antagonist verapamil has been shown to affect a variety of other ion channels as well as neurotransmitter receptors. We report that verapamil reversibly inhibits binding of the nicotinic receptor probe 125 I-α-bungarotoxin to membranes from rat brain, Torpedo californica , the rat pheochromocytoma cell line PC12 and the human medulloblastoma cell line TE671, with K i values of 24.0, 90.5, 165.4 and 869.6 μM, respectively. These effects are calcium independent and insensitive to a variety of organic and inorganic calcium channel antagonists. While Hill coefficients suggest mechanistic differences for verapamil action in the tissues examined, derivative graphical analysis demonstrates a common mechanism of heterotypic, allosteric inhibition. Verapamil may be useful as a probe to elucidate aspects of receptor-effector coupling.