Article

Therapeutic approaches to ion channel diseases.

Division of Pharmacology, Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Bari, Italy.
Advances in genetics (impact factor: 3.39). 02/2008; 64:81-145. DOI:10.1016/S0065-2660(08)00804-3 pp.81-145
Source: PubMed

ABSTRACT 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.

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Keywords

alternative splicing
 
complex cellular functions
 
different subunits increase tremendously
 
drug development
 
encode ion channel subunits
 
heteromeric assembly
 
intense research
 
intimate drug-channel interaction
 
ion channel diseases
 
ion channel genes
 
ion channel pharmacology
 
ion channel subtypes
 
ion channels
 
molecular pharmacology
 
new drugs
 
newest aspect
 
pathological processes
 
recent advancement
 
stringent definition
 
target ion channels