The β1 Sodium Channel Subunit Modifies the Interactions of Neurotoxins and Local Anesthetics with the Rat Brain IIA α Sodium Channel in Isolated Membranes but not in Intact Cells

Mammalian brain sodium channels consist of an α subunit and two smaller β subunits. The role of the β1 subunit in modulating ligand interactions at these channels was examined using a cell line stably expressing human β1 and rat brain IIA α subunits. Coexpression of the β1 subunit had no effect on the potencies of sodium channel blockers in inhibiting whole cell [3H]batrachotoxinin A benxoate ([3H]BTX) binding or veratridine-stimulated [14C]guanidinium influx. Coexpression of the β1 subunit also had no effect on the potencies of α scorpion toxin, brevetoxin, or RU 39568 in stimulating [14C]guanidinium influx. By contrast, coexpression of the β1 subunit had dramatic effects on ligand interactions in isolated membranes. In isolated membranes of cells expressing only the α subunit, the neurotoxins had no stimulatory effect on [3H]BTX binding and the potencies of local anesthetic-like channel inhibitors were 10–100-fold lower than those at native sodium channels. Whereas in membranes of cells coexpressing the β1 subunit, the neurotoxins increased [3H]BTX binding 30-fold and the potencies of the sodium channel inhibitors closely matched those found at native sodium channels. These findings indicate that the β1 subunit is not required for the binding of sodium channel activators or inhibitors but rather, that the β1 subunit may stabilize the α subunit in a functional conformation thereby allowing detection of these interactions in disrupted membranes. Copyright © 1996 Elsevier Science Ltd.