Lidocaine has different effects and potencies on muscle and brain sodium channels

Multiple open channel states revealed by lidocaine and QX-314 on rat brain voltage-dependent sodium channels.

“…1 B) (Strichartz, 1973;Moczydlowski et al, 1986b). As previously reported (Salazar et al, 1995) in brain channels, the level of the lidocaine-induced fast-open channel block was not constant; that is, there were periods during which the level of the lidocaine-induced open channel block was greatly reduced ( Fig. 1 A, right).…”

“…We have previously reported that brain-but not muscle-derived sodium channels showed periods during which there was a relief in the level of the lidocaineinduced open channel block, as though the open chan-nel state displayed changes in its lidocaine apparent binding affinity (Kd) (Salazar et al, 1995). In this report we further characterize the changes in K a values to investigate whether the underlying mechanism could be the presence of spontaneously occurring conformational changes of the fully open channel state.…”

“…Planar lipid bilayers were formed with a mixture of neutral phospholipids, and the channels were incorporated as previously described (Salazar et al, 1995). The compartments on either side of the Teflon partition (1 ml capacity) contained symmetrical 0.5 M or 0.2 M NaC1.…”

“…Moreover, functional studies indicated that channel structural differences between brain-and muscle-derived channels affect the apparent binding affinity of some local anesthetics such as lidocaine (Salazar et al, 1995) but not of other local anesthetics such as cocaine (Wang, 1990). On the other hand, the location, with respect to the intracellular channel aspect, of the binding site mediating the local anesthetic-induced open channel block seems to be the same in brain-and muscle-derived channels (Salazar et al, 1995;Wang, 1990).…”

“…One approach that facilitates the study of this local anesthetic effect is incorporating batrachotoxin (BTX)Lmodified sodium channels into planar lipid bilayers (Krueger et al, 1983). Because BTX modifies the channel inactivation process in such a manner that the channel remains open almost continuously at potentials more positive than -50 mV (Moczydlowski et al, 1984) and because of the high stability of the planar lipid bilayers, one can observe the channels for long periods (>30 min) both during con-trol and in the presence of the anesthetic (Salazar et al, 1995). With this method, it has been shown that local anesthetics block the open state of BTX-modified sodium channels in a way that is consistent with their binding to a single site (Moczydlowski et al, 1986b;Wang, 1988;Zamponi et al, 1993a).…”