Conservation of Ligand Binding Between Voltage-Gated Sodium and T-Type Calcium Channels

In vertebrates, two types of ion channels are responsible for amplifying electrical signals and facilitating neurotransmission: voltage-gated sodium (Nav1) and calcium (Cav3) channels. When the cell membrane is moderately depolarized, these channels allow the rapid influx of their respective ions – Na+ and Ca2+. Nav1 and Cav3 channels are structurally related, and their expression overlaps in various excitable tissues, such as muscles and neurons. Dysfunction of these depolarization-activated cation channels can lead to various diseases including neuropathic pain, epilepsy, atrial fibrillation, and cancer. Hence, compounds that can modulate the function of both Nav1 and Cav3 channels have the potential to be used as therapeutic agents. This chapter will primarily focus on venom-derived peptide toxins and small molecules that dually affect Nav1 and Cav3 channels.