Therapeutic approaches to ion channel diseases.
More than 400 genes are known that encode ion channel subunits. In addition, alternative splicing and heteromeric assembly of different subunits increase tremendously the variety of ion channels. Such many channels are needed to accomplish very complex cellular functions, whereas dysfunction of ion channels are key events in many pathological processes. The recent discovery of ion channelopathies, which, in its more stringent definition, encloses monogenic disorders due to mutations in ion channel genes, has largely contributed to our understanding of the function of the various channel subtypes and of the role of ion channels in multigenic or acquired diseases. Last but not least, ion channels are the main targets of many drugs already used in the clinics. Most of these drugs were introduced in therapy based on the experience acquired quite empirically, and many were discovered afterward to target ion channels. Now, intense research is being conducted to develop new drugs acting selectively on ion channel subtypes and aimed at the understanding of the intimate drug-channel interaction. In this review, we first focus on the pharmacotherapy of ion channel diseases, which includes many drugs targeting ion channels. Then, we describe the molecular pharmacology of ion channels, including the more recent advancement in drug development. Among the newest aspect of ion channel pharmacology, we draw attention to how polymorphisms or mutations in ion channel genes may modify sensitivity to drugs, opening the way toward the development of pharmacogenetics.
Camerino
Diana Conte
DC
Division of Pharmacology, Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Bari, Italy.
Desaphy
Jean-François
JF
Tricarico
Domenico
D
Pierno
Sabata
S
Liantonio
Antonella
A
D001327:Autoimmune Diseases / Q000628:therapy; D053447:Channelopathies / Q000628:therapy*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008305:Malignant Hyperthermia / Q000503:physiopathology / Q000628:therapy; D018482:Muscle, Skeletal / Q000503:physiopathology; D009135:Muscular Diseases / Q000628:therapy*; D009222:Myotonia / Q000188:drug therapy / Q000503:physiopathology; D009223:Myotonic Dystrophy / Q000188:drug therapy / Q000503:physiopathology; D020511:Neuromuscular Junction Diseases / Q000503:physiopathology / Q000628:therapy*; D015221:Potassium Channels / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology
D007473:Ion Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels