Characterization, localization and pharmacological profile of a high-affinity [3H]lidocaine binding site

Electrophysiological findings support the existence of voltage-dependent, sodium channel-associated receptors for class I antiarrhythmics. We have tried to identify such receptors with tritiated lidocaine. High-affinity binding sites were discovered in heart and brain membranes, but liver and kidney particulate fractions had the highest density of sites. The dissociation constants were 75 nM in bovine heart and 29 nM in guinea-pig liver membranes. Binding was reversible (t 1/2: 102 s at 2 degrees C), optimal at pH 9-10 and was only partly destroyed by heat treatment. Subcellular fractionation experiments excluded a plasmalemmal association of the lidocaine site in heart. The competition profile of 16 antiarrhythmics indicated chemical comparability of the sites in heart and liver. These data greatly challenge the applicability of labeled lidocaine as sodium channel probe. The pharmacological significance of the site described here remains to be clarified.