Editorial [Hot Topic:Ion Channels as a Target for Drug Design (Executive Editor: Kwok-Keung Tai)]

Ion channels are a class of integrated membrane proteins that allow selective ion permeation across biological membranes and are vital for signal transductions within the cell and between the cells. Because channels are involved in a variety of physiological functions, they are potential targets for therapeutic intervention. This issue of Current Pharmaceutical Design consists of seven review articles describing the roles of several ion channels in a variety of biological functions. GABA is a major inhibitory neurotransmitter in the central nervous system. Neuronal activities are inhibited when GABA receptors are activated by GABA. GABA receptors are chloride ion channels and are major therapeutic target for general anesthetics. In the first article, Drs. Birin and Korpi [1] review the structure-function relationship of GABAA receptors; the differences in the properties between recombinant GABAA receptors and those in native tissues. The effects of accessory proteins in modulation of GABAA receptors activities are also discussed. Voltage-gated potassium channels also regulate cell membrane excitability in neurons by controlling the flow of potassium ions through the membrane in response to the changes in membrane potential. In the second article, Drs. Cai and Sesti [2] review the role of β-subunit, phosphorylation in modulation of the A-type potassium channels including the newly discovered mode of regulation of channel activities by enzymatic action of beta-subunits using an invertebrate animal model system. Sustained stimulation of the NMDA receptor channels in the brain during cerebral hypoxia causes excitotoxic injury. This NMDA receptormediated excitotoxic injury could also play a role in the pathogenesis of a number of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In the third article, Dr. Albensi [3] describes the structure and the role of the NMDA receptor channels in modulation of synaptic plasticity and excitotoxicity; developmental changes of the NMDA receptor channels and the classification of NMDA receptor channel blockers. Anti-arrhythmic drugs are one of the mechanistically best understood ion channel-targeted therapeutics. Most of the current anti-arrhythmic agents act on cell surface ion channels. Recent evidence have showed that perturbations in intracellular calcium release as a result of acquired or genetic defects in the ryanodine receptor channels located in the sarco/endoplasmic reticulum could trigger cardiac arrhythmias. Drs. George and Lai [4] review the structure of ryanodine receptor channels; the cellular and molecular mechanism of how the dysfunctions of intracellular ryanodine receptor channels causing lethal arrhythmias, and how the advancement of this knowledge enhances the development of novel anti-arrhythmic strategies is discussed. Water is a main constituent of all living organisms. Water molecules permeate biological membranes through the water channels or aquaporins. Dr. Yool [5] reviews the role of aquaporins in water homeostatsis in the peripheral vascular endothelia and in the brain. She discusses the role of aquaporins in cell migration which is essential for an array of biological processes such as angiogenesis and tumorigenesis. The structure-function relationships and the gating mechanisms of aquaporins are also reviewed. The potential therapeutic implications of molecules that can modulate water permeation through aquaporins are discussed.......