How do local anesthetics bind to the sodium channel?

Local anesthetics bind preferentially to the inactivated state of the sodium channel due to the nature of their mechanism of action. When a nerve cell is depolarized, sodium channels transition through different states: resting, active, and inactivated.

Local anesthetics are designed to penetrate the nerve membrane while the sodium channels are in their inactivated state. This is significant because when the channels are inactivated, they are unable to open and allow sodium ions to enter the cell, which is essential for the generation and propagation of an action potential. By binding to these inactivated channels, local anesthetics effectively block nerve conduction. This is particularly effective under conditions of repetitive stimulation when many sodium channels are inactivated.

This binding mechanism is crucial for the action of local anesthetics. Their affinity for the inactivated state ensures that they can effectively prevent the transmission of pain signals during surgical procedures or any invasive interventions that may cause discomfort.