Lidocaine

Voltage-gated Na⁺ channels (VGSC, Na_V) are critically important for electrogenesis and nerve impulse conduction, and are targeted by clinically relevant analgesics such as Lidocaine¹. Certain Na_V channel isoforms are predominantly expressed in peripheral sensory neurons associated with pain sensation, and the expression and functional properties of these channels can be dynamically regulated following axonal injury or peripheral inflammation².

Lidocaine is a commonly used local anesthetic as well as an antiarrhythmic drug, which is a potent and selective blocker of Na_V channels³. It inhibits, for instance, human Na_V1.5 channels expressed in Xenopus oocytes in a positive rate-dependent and concentration-dependent manner, with an IC₅₀ value of 145.6 µM⁴. Its block can be complex, exhibiting channel state-dependent and time-dependent elements⁵.

Reports on the effects of Lidocaine suggest that although the drug is somewhat selective in voltage-clamp experiments (the drug blocks TTX-sensitive currents at concentrations that are approximately fourfold lower than those that block high-threshold TTX-resistant currents), its functional discrimination is likely to be poor. Lidocaine block of TTX-sensitive currents indicates an IC₅₀ value between 40 and 50 µM using protocols that incorporate a negative holding potential^6-7. This block of high-threshold TTX-resistant currents has a reported IC₅₀ of approximately 200 µM using similar protocols. The channel state-dependence of TTX-resistant current block has been demonstrated by a depolarization that maximally activates the current. Under these circumstances the IC₅₀ decreases to 60 µM.^6-7