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

Ion channels play a pivotal role in transmembrane cell signaling. Their involvement in a variety of physiological functions and in diseases means that they are an important target for therapeutic intervention. This issue of Current Pharmaceutical Design is dedicated to the topic "Ion Channels as a Target for Drug Design". In the first article, Nelson et al. [1] review low-voltage activated, or T-type calcium channels in synaptic integration and in nociception. These T-type calcium channels are potential targets for the therapy of epilepsy and pain. In the second article, Panyi et al. [2] discuss the role of Kv1.3 and calcium-activated potassium channels (IKCa1) in T cell activation and the development of their inhibitors. Such inhibitors have therapeutic potential for a number of diseases that involve T cell activation such as multiple sclerosis and type I diabetes mellitus. In the third article, Sagnella and Swift [3] review a renal epithelial sodium channel and its role in hypertension, one of the main causes of mortality in industrialized nations. In the fourth article, Verkman et al. [4] describe the identification of small molecule inhibitors of cystic fibrosis transmembrane conductance regulator (CFTR) and the activators of a common mutant of CFTR causing cystic fibrosis. These inhibitors can potentially be used for the therapy of secretory diarrheas, while activators can be employed for the therapy of cystic fibrosis. In the fifth article, Shoshan-Barmatz et al. [5] give an account on the mitochondrial voltage-dependent anion channel (VDAC) including features of channel activity and the role of VDAC in apoptosis. In the sixth article, Thomas et al. [6] review the human ether-a-go-go-related gene (hERG) potassium channels, which carry the rapid component of the cardiac repolarization current, and hence cardiac rhythm. This article covers many aspects of hERG channels including some novel antiarrhythmic strategies that involve modulating the cardiac IKr current carried by hERG channels. It is now known that most pore-forming α-subunits of ion channels require some ancillary subunits in the channel complex in order to serve specific physiological roles in vivo. In the final article, Panaghie and Abbott [7] review how some ancillary subunits modulate the functional attributes and pharmacology of some voltage-gated potassium channels, which are important in the repolarization of all excitable cells. In particular, the impact of ancillary subunits on the development of therapeutics targeting ion channels is discussed. We would like to thank all of the contributors - it is their commitment that has made this issue possible. References [1] Nelson MT, Todorovic SM, Perez-Reyes E. The Role of T-type Calcium Channels in Epilepsy and Pain. Curr Pharm Des 2006; 12(18): 2189-2197. [2] Panyi G, Possani LD, Rodríguez de la Vega RC, Gáspár R, Varga Z. K+ Channel Blockers: Novel Tools to Inhibit T Cell Activation Leading to Specific Immunosuppression. Curr Pharm Des 2006; 12(18): 2199-2220. [3] Sagnella GA, Swift PA. The Renal Epithelial Sodium Channel: Genetic Heterogeneity and Implications for the Treatment of High Blood Pressure. Curr Pharm Des 2006; 12(18): 2221-2234. [4] Verkman AS, Lukacs GL, Galietta LJV. CFTR Chloride Channel Drug Discovery - Inhibitors as Antidiarrheals and Activators for Therapy of Cystic Fibrosis. Curr Pharm Des 2006; 12(18): 2235-2247. [5] Shoshan-Barmatz V, Israelson A, Brdiczka D, Sheu SS. The Voltage-Dependent Anion Channel (VDAC): Function in Intracellular Signalling, Cell Life and Cell Death. Curr Pharm Des 2006; 12(18): 2249-2270. [6] Thomas D, Karle CA, Kiehn J. The Cardiac hERG/IKr Potassium Channel as Pharmacological Target: Structure, Function, Regulation, and Clinical Applications. Curr Pharm Des 2006; 12(18): 2271-2283. [7] Panaghie G, Abbott GW. The Impact of Ancillary Subunits on Small-Molecule Interactions with Voltage-Gated Potassium Channels. Curr Pharm Des 2006; 12(18): 2285-2302.