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What is Ion Channel Research

Ion Channels

Ion channels are pore-forming proteins found in virtually every cell in the human body. They are intimately involved in process within the body including secretion, contraction, and communication within and between cells and tissues. Ion channel dysfunctions ("channelopathies") have been implicated in many diseases. At ICBC we are interested in diseases of smooth muscle origin, where ion channel modulation could be helpful.

Ion channels control charge distribution/regulation (electrical potential) across membranes and regulate the transport of ions or charged particles such as sodium, calcium, potassium and chloride to and from the cell. Most switch between conducting and non-conducting states and can selectively transmit or block a particular ion species, affecting contractility, secretion and many other specialized and general cell functions.

Ion channels are ideal targets for drug discovery, as their opening and closing can be modulated by drugs, which in turn can cause an increase or decrease of ion flow through the channels. This is a result of various “gating” mechanisms used by ion channels to open and close their pores in response to biological stimuli including change in shape (conformational changes) as a result of ligands binding to them, or changes in membrane potential or charge distribution across the cell membrane. A complex interaction of charge, ion distribution, ligand binding and other factors lead to changes in ion channel gating, activation states (open, closed, activated, deactivated, inactivated) and as a result, changes in cellular activity, contractility, secretion and a variety of biological functions.

New generations of drugs are being developed which selectively block the channels in a specific state, such as frequent activation/deactivation configurations such as would occur in an overactive tissue.Ion channel modulators include 15 of the top 100 drugs, and generate almost €10 Billion in revenues annually. Blockbusters such as Norvasc (hypertension), Ambien (insomnia) and Xanax (anxiety) have shown how lucrative ion channels as therapeutic targets can be. ICBC is at the leading edge in the race to design more specific small molecule inhibitors that differentiate between channel physiologic states (open, closed, or inactivated) , advances in the identification of subtype-selective blockers and creation of novel cell lines to enhance safety profiling and selectivity of drugs.

Skill Sets and Resources

With talented scientists working in multidisciplinary teams, skill sets include whole tissue contractility studies, live cell imaging, immunohistochemistry, cell staining, electrophysiology, molecular biology, synthetic and medicinal chemistry. Facilities include an electrophysiology laboratory with 6 patch clamp and intracellular rigs, two cellular imaging laboratories with 5 Nipkow Confocal rigs and a Zeiss Meta righ, a synthetic and medicinal chemistry laboratory, a molecular biology suite, a whole tissue laboratory and a small animal facility.

We work closely with industry, and are led by an industry Steering Committee to ensure we are up-to-date with the latest trends and technologies. High quality collaborations reinforce our position as partner of choice in ion channel biologym helping us achieve our mission and building on this nucleus of world class research by attracting investment and partners to the region.

 

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