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Background The local anesthetic lidocaine is generally believed to reach its binding site in the intracellular vestibule of the voltage-gated sodium channel via the cell membrane. QX222 is a permanently charged, quaternary amine analogue of lidocaine, which can access this binding site via a hydrophilic route across the channel protein. The mutation I1575E of the adult rat muscle-type sodium channel (rNaV1.4) opens such a hydrophilic pathway. When bound to the internal vestibule, 500 μM lidocaine stabilize both fast and slow inactivated states. We have tested if QX222, once bound to the internal vestibule of I1575E mutant channel, exerts a similar modulatory action on inactivated states as lidocaine.

Differential modulation of rNaV1.4 channel inactivated states by lidocaine and its charged analogue QX222