Biological and Medicinal Chemistry

Light-Induced Control of Voltage Gated Ion Channels



Voltage gated ion channels are transmembrane proteins responsible for the generation and propagation of action potentials in excitable cells. They are key targets in receptor pharmacology, since the simple actions of opening and closing their pore with different kinetics or conductivity have been associated with a large number of channelopaties. Crystal structures of ion channels became available only in the last decades and, in combination with mutagenesis data, allowed the identification of drugs able to modulate ion conduction. However, most of the traditional modulators are not selective and present adverse side effects. Photopharmacology is establishing a new approach to overcome the problem of selectivity often present in voltage gated ion channels due to highly conserved binding regions among channels of the same subfamily. In this review, we describe the central pore region of Voltage gated sodium and potassium channels from a structural and pharmacological perspective, characterizing the binding mode of natural toxins and synthetic compounds able to physically occlude ion conduction. In addition, a bridge is created between classical pharmacology and photopharmacology, describing the approaches aimed to control the activity of voltage gated ion channels by photosensitive drugs.


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