Selective modification of sodium channel gating by solvents and drugs

In Myxicola heavy water (D2O) does not alter Na+ gating currents, but slows activation and inactivation. In this study, the solvent formamide (5-20% v/v) is shown to proportionately and reversibly block Na+ currents and charge movement, suggesting it may be useful for fractionating gating currents. Formamide- and prepulse-sensitive (inactivating) gating currents were identical, comprising 60-80% of total charge. Both had rising phases and decayed as single exponential functions. Formamide-insensitive and non-inactivating charge movements had no rising phases and decayed slowly with more complex kinetics. Another solvent, dimethylsulfoxide (1% v/v), had no effect on Na+ activation or charge movement, though it did affect inactivation. Amantadine (0.1 mM) did not change Na+ activation or charge movement, but slowed inactivation and shifted the foot of the steady state Na+ inactivation curve. Sotalol (0.1 mM) slowed inactivation, but also inhibited Na+ activation and gating current.