TABLE 4

Effect of free local anesthetic, antiarrhythmic, or anticonvulsant VGSC inhibitors on the dissociation of compound 4 from hNa_v1.5 VGSCs

hNa_v1.5-293-EBNA cells were incubated with compound 4 (10 μM), as described under Materials and Methods, to elicit full occupancy of the hNa_v1.5 VGSCs. At the end of the stimulus train, compound 4 was washed out and replaced with VGSC inhibitor (at the concentrations specified), or drug-free extracellular buffer (control), for a 5-min chase period. Current magnitude was monitored (at a frequency of 0.2 Hz) throughout the duration of the inhibitor application and for an additional 5-min washout period, with drug-free extracellular buffer. The extent of recovery of the hNa_v1.5 Na⁺ current, relative to the initial current amplitude, was determined at the end of the 5-min washout. Tonic and phasic IC₅₀ values, for the various VGSC inhibitors, were determined using the standard protocol, described in the methods (n > 3 cells). Recovery data represents mean ± S.E.M. (n > 3 cells).