Voltage-sensitive ion channels are a class of transmembrane proteins that provide a basis for cellular excitability and the ability to transmit information via ion-generated membrane potentials. In response to changes in membrane potentials, these molecules mediate rapid ion flux through selective channels in a cell membrane. If channel density is high enough, a regenerative depolarization results, which is called an action potential.
The voltage-gated sodium channel is responsible for the generation and propagation of action potentials in most electrically excitable cells, including neurons, heart cells, and muscle. Electrical activity is triggered by depolarization of the membrane, which opens channels through the membrane that are highly selective for sodium ions. Ions are then driven intracellularly through open channels by an electrochemical gradient. Although sodium-based action potentials in different tissues are similar, electrophysiological studies have demonstrated that multiple structurally and functionally distinct sodium channels exist, and numerous genes encoding sodium channels have been cloned. The SCN1A gene belongs to a gene family of voltage-gated sodium channels.
There is a long standing need to diagnose and/or treat pathologies relating to impaired electrical excitability involving sodium channel dysfunction resulting from injury, genetic abnormalities, or disease states. In particular, sodium channel dysfunction is associated with epilepsy, convulsion, pain (including chronic pain), neuronal damage resulting from ischemia, and neuronal degeneration.
To address this need, the present invention provides in one embodiment a method for identifying molecules that specifically bind to a sodium channel and/or regulate sodium channel activity. The method employs a system for heterologous expression of a human sodium channel as disclosed herein.