Voltage & Ligand Gated Ion Channels
Ion channels play an important role in cell signaling, electrical excitability, and fluid transport, and are drug targets for diseases such as heart disease, diabetes, autoimmune diseases, and migraine. As membrane spanning proteins, ion channels facilitate the rapid movement of ions across the cell membrane down their electrochemical gradient. They play a vital role in neuronal signal transduction, neurotransmitter release, muscle contraction, cell secretion, enzyme activation, signal transduction, and gene transcription. To date, more than 300 different human ion channel genes have been identified.
Ion channels can be grouped into two classes, voltage- and ligand- gated channels, and can exist in multiple states such as the closed, open, and inactivated states. Voltage-gated ion channels transition between these states in response to changes in membrane potential, while ligand-gated channels transition between these states in response to the binding and unbinding of a ligand. In the open state, ions can flow through a single ion channel pore at rates of over 107 ions per second.
The role of ion channels in drug safety is also well recognized. Since 1985, five drugs have been withdrawn from market due to their adverse cardiac effects. The mechanisms underlying this toxic effect involve inhibition of one or more of the cardiac ion channels.
Traditional methods for primary and secondary screens of ion channels, such as binding, ion flux, and fluorescent probes, measure ion channel activity indirectly. Patch clamp electrophysiology is regarded as the gold standard for measuring ion channel activity directly. It enables real time measurement of ion channel activity but in its traditional format is low throughput and requires a high degree of operator skill. As a result, until recently, drug screening assays for ion channels, in comparison to those for enzyme and receptor targets, have had to compromise data quality for throughput.
Molecular Devices began to change all of this in 2002 when it introduced the first commercially-available automated electrophysiology system, and has continued to meet the needs of drug discovery researchers by introducing higher and higher throughput systems with greater and greater capabilities. To learn more about how our automated electrophysiology systems can help advance your ion channel drug discovery efforts, click on the appropriate link below.
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