Voltage -gated potassium channels: not very exciting?

Of the transmembrane proteins found in the semi-permeable lipid bilayers of all cells, voltage gated K+ channels are arguably among the most important. K+ channels set the membrane potential, control excitability, and regulate the extracellular K+ concentration. In this presentation I will describe how K+ channels carry out their roles, and their importance in health and disease. We are currently working on the human hERG or Kv11.1 channel (human Ether-à-go-go-Related Gene- KCNH2). This is a particularly interesting channel as it is responsible for setting the cardiac rhythm by driving the inter-beat interval. Mutants cause ‘long QT syndrome’ leading to cardiac arrhythmia and death. I will discuss the spectacular failure of Cisapride, a drug designed to target serotonergic receptors in gastrointestinal malfunction, which unfortunately turned out to one of the most effective hERG blockers we currently have. I will explain how and why hERG channels are now widely used in drug discovery and safety testing.