The molecular interaction between local anesthetic/antiarrhythmic agents and voltage-gated sodium channels

Local anesthetic/antiarrhythmic agents render their therapeutic effects via suppression of ionic current through voltage-gated Na channels. Recent work to understand the molecular basis of this drug-receptor interaction has exploited the combined technologies of molecular biology and electrophysiology. Despite the complexity of the effects of site-directed mutations on Na channel function and local anesthetic action, some consistent themes are emerging. Recent studies suggest that the local anesthetic compounds actively promote channel inactivation and, in doing so, function as allosteric effectors. Although the charged moiety may enter the Na channel pore, the primary mechanism whereby local anesthetic agents reduce excitability may be to induce channel inactivation.