Lidocaine. A State Dependent Nav Channel Inhibitor.
Voltage-gated Na+ channels (VGSC, Nav) are critically important for electrogenesis and nerve impulse conduction, and as targets for important clinically relevant analgesics such as Lidocaine.
Certain NaV channel isoforms are predominantly expressed in peripheral sensory neurons associated with pain sensation, and the expression and functional properties of Nav channels in peripheral sensory neurons can be dynamically regulated following axonal injury or peripheral inflammation. Lidocaine is a commonly used local anesthetic as well as an antiarrhythmic drug, which is a potent and selective blocker of Nav channels. It inhibits, for instance, human Nav1.5 channels expressed in Xenopus oocytes in a positive rate-dependent and concentration-dependent manner, with an IC50 value of 145.6 μM.
Its block can be complex, exhibiting channel state-dependent and time-dependent elements.
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 of between 40 and 50 μM using protocols that incorporate a negative holding potential. This block of high-threshold TTX-resistant currents has a reported IC50 of about 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.
Ion Channel Modulators; Voltage - Gated Na+ Channel Blockers.
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