Welcome to “Ion Channels: Key Therapeutic Targets”

Voltage and ligand-gated channels mediate key physiological functions in a wide range of excitable and nonexcitable tissues. By their very nature, ion channels are designed to regulate the electrical activities of cells, however, they also have the propensity to regulate cell-signaling events. This is especially true for ion channels that are calcium permeable, as calcium ions trigger a host of cellular responses that range from the release of neurotransmitters to the activation of gene transcription. Ion channels should not be viewed as isolated entities, but rather as team players that work together to produce a desired cellular output. As a result, ion channel therapeutics may not only affect their main target, but can be exploited to indirectly regulate the activities of other channels. On the flip side, ion channels are implicated in various disorders that can arise from mutations in ion channel genes, or simply due to misregulation of channel activity. As a result, many types of channels have become prime targets for therapeutics. Compared with drugs that act on G protein-coupled receptors and that thus broadly affect cell signaling, ion channel-selective inhibitors have the potential for more precise intervention and, therefore, remain attractive drug candidates.

In this issue

This thematic issue of Future Medicinal Chemistry highlights a selection of recent advances in the molecular pharmacology of ion channels. Terstappen and colleagues focus on novel screening technologies for ion channel drugs. The methodology paper by Devor et al. focuses on the development of a novel immunofluorescence assay to detect calcium-activated potassium channels in the plasma membrane. These articles are complemented by an editorial by Farre and Fertig, who briefly discuss the use of automated patch clamp systems in drug-discovery research. In his editorial, de Groot provides a commentary on the usefulness of computational approaches in ion channel drug discovery.

The issue also features review articles that discuss ion channels as targets for drugs in a number of different pathophysiological conditions. Teichert and Olivera provide an interesting discussion on the role of natural products as ion channel therapeutics, focusing on peptide-based compounds derived from toxic marine species. Two articles focus on potassium channels: Stühmer and Pardo give a broad overview of the role of potassium channels in cancer cells and their suitability as anticancer drug targets; while Denton et al. look at small-molecular modulators of inwardly rectifying potassium channels with a focus on the development of novel diuretics. Voltage-gated calcium and sodium channels are addressed in articles by England and Rawson, and Belardetti. The former focus on sodium channel isoform-dependent drugs in the context of pain. Belardetti provides an additional perspective on the possible role of calcium channel blockers in the treatment of alcohol abuse.

More broadly, ion channels as putative drug targets for pain are also addressed by Pevarello et al.; whereas Wickenden et al. more specifically address pain in the context of TRPA1 channels. In the area of ligand-gated ion channels, Dunn and colleagues focus on the molecular physiology and pharmacology of the GABA_A receptor, a key drug target for benzodiazepines. Lastly, Mellor discusses AMPA receptors and their potential as therapeutic targets for a wide range of disorders.

These articles provide a glimpse into the rapidly evolving world of ion channels as drug targets and underscore their important role in therapeutic interventions for a variety of disorders and across a range of different organ systems.

Finally, I would also like to alert readers to ‘Clinical Pharmacology of Ion Channels’, a complementary thematic issue published this month in this journal’s sister title Expert Review of Clinical Pharmacology[1]. Together these thematic issues will serve as an instructive resource for all those interested in the development of this exciting field.

I invite all readers to enjoy this exciting issue!

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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Funding

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.