Editorial [Hot Topic: Ion Channels: Applications in Ion Channel Drug Discovery(Guest Editor: Douglas S. Krafte)]

Ion channel proteins are fascinating molecules that play key roles in many physiological processes. In fact, no mammalian cell type has been identified which does not express a complement of ion channel proteins. However, while all cell types express ion channels, the specific role these channels play can vary significantly. In excitable cells such as neurons, skeletal muscle and heart, ion channels act as molecular switches to either trigger excitation or reset the membrane potential to a baseline, resting level depending on which type of ion channel is activated. In non-excitable cells, channels can play other roles such as regulation of fluid movement, salt secretion or resorption, and triggering of signal transduction cascades that eventually lead to gene transcription. Over the past several years, there has been an explosion of data elucidating the role of specific channels in genetic disorders due to mutations which typically affect gating and/or expression. These ‘channelopathies’ further validate the role various ion channels play in maintaining normal physiological processes. The genetic data also suggest that modulation of ion channel function is a good means to intervene in pathophysiological processes and restore normal function. One good example of the genetics leading to a greater understanding of the role for a particular channel is a series of mutations in Kv7 channels that cause a neonatal seizure disorder [1]. The genetic data highlight the key role of these channels in regulating CNS excitability, and since decreases in channel expression lead to seizures activation of Kv7 channels may be a useful therapeutic approach to treating epilepsy [2]. Many other examples in a variety of diseases or disorders also exist including pain, myotonias and arrhythmia [3-5]. Channelopathies as a whole have been nicely reviewed by Ashcroft [6]. Given the key role ion channels play in health and disease and the wealth of new data validating various ion channel subtypes as possible therapeutic drug discovery targets, there has been something of a resurgence in ion channel drug discovery. Facilitating this resurgence have been advances in the technology available to academic and industrial scientists, which can be applied to investigate ion channel pharmacology [7]. In this volume, we have included reviews and original research by a number of investigators who are at the forefront in the development and/or application of new technologies for the characterization of ion channel function and pharmacology. The volume begins with an excellent review on the ion channel genome, which describes the landscape with respect to potential molecular targets for drug discovery, relevant comparisons across species and thoughts regarding the potential for overlapping pharmacology among gene families. The remainder of the volume describes several of the most widely applied technologies available to the research community including planar patch clamp technology, advanced semi-automated micropipette applications, use of voltage-sensitive dyes, and high-throughput Xenopus oocyte recordings. In addition, a number of the articles focus on real-world experiences from pharmaceutical/biotech investigators applying several of these technologies in an industrial setting. While all available methods and/or instrumentation can not be covered in a single volume, the articles cover many of the most widely used approaches and the investigators report their experiences and suggest how best to make progress using these technologies in a research setting and/or a drug screening environment. We hope the readers find the articles informative and helpful in advancing their own ion channel research and drug discovery programs.