RESUMO
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 Kv 3.1 and Kv 1.1 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 Kv 3.1 channels natively expressed in SH-SY5Y cells and Kv 1.1 channels expressed in HEK 293 cells. RESULTS: Lidocaine reversibly inhibited Kv 3.1 and Kv 1.1 channels in a concentration-dependent manner. The half-maximal inhibitory concentration for conductance block was 607 micromol/L for Kv 3.1 (n=47) and 4,550 micromol/L for Kv 1.1 channels (n=56), respectively. The Hill coefficients were 0.9 and 0.8. Conductance block was voltage dependent for Kv 3.1 but not for Kv 1.1 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 micromol/L) or induction (>1-2 mg/L; >3.5-7 micromol/L) of tinnitus Kv 3.1 and K v1.1 channels would be suppressed by at most 1.5 to 2%. CONCLUSION: Human Kv 3.1 and Kv 1.1 channels exhibited different sensitivities to the inhibitory action of lidocaine. The small effect at clinically relevant concentrations suggests that the physiologic roles of Kv 3.1 and Kv 1.1 channels in auditory neurons seem not to be impaired during the therapeutic or diagnostic application of lidocaine in the auditory system.