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Differential Lidocaine Sensitivity of Human Voltage-gated Potassium Channels Relevant to the Auditory System

Hypothesis: Lidocaine may lead to an alteration in the processing of hearing as observed during tinnitus by inhibiting voltage-gated potassium channels at clinically relevant concentrations. Background: Recent molecular evidence suggests that the voltage-gated potassium channels Kv3.1 and Kv1.1 play an important functional role in the auditory system. Lidocaine is known to influence the auditory system and may thus exert pharmacological effects on these human potassium channels. Methods: Patch-clamp recordings were performed on the pharmacologic action of lidocaine on Kv3.1 channels natively expressed in SH-SY5Y cells and Kv1.1 channels expressed in HEK293 cells. Results: Lidocaine reversibly inhibited Kv3.1 and Kv1.1 channels in a concentration-dependent manner. The half-maximal inhibitory concentration for conductance block was 607 μmol/L for Kv3.1 (n = 47) and 4,550 μmol/L for Kv1.1 channels (n = 56), respectively. The Hill coefficients were 0.9 and 0.8. Conductance block was voltage dependent for Kv3.1 but not for Kv1.1 channels. The midpoint of current activation of both channels was shifted to hyperpolarized potentials. At free plasma concentrations determined during suppression (0.5-1 mg/L; 1.75-3.5 μmol/L) or induction (>1-2 mg/L; >3.5-7 μmol/L) of tinnitus Kv3.1 and Kv1.1 channels would be suppressed by at most 1.5 to 2%. Conclusion: Human Kv3.1 and Kv1.1 channels exhibited different sensitivities to the inhibitory action of lidocaine. The small effect at clinically relevant concentrations suggests that the physiologic roles of Kv3.1 and Kv1.1 channels in auditory neurons seem not to be impaired during the therapeutic or diagnostic application of lidocaine in the auditory system.