Ion Channels

Group Leaders:

Our research is focussed on understanding the intimate relationship between ion channel structure and function. The objectives are to understand how and why ion channels do what they do i.e. to understand their molecular mechanism of operation at an atomic level as well as understanding their role in physiology and disease. As a model system we work primarily with the inwardly-rectifying family of potassium channels or ‘Kir’ channels. The human genome contains fifteen different Kir channel genes divided into seven major subfamilies (Kir1.0-Kir7.0). Like other potassium (K+) channels, Kir channels function as tetramers with each subunit contributing to the pore of the channel. Each individual subunit has two transmembrane (TM) domains and large cytoplasmic domains which are involved in the response of Kir channels to factors such as G-proteins, PIP2, ATP and intracellular pH. Kir channels are therefore able to regulate cellular electrical activity and K+ transport processes by coupling channel activity to a wide range of metabolic and physiological stimuli. Their importance is illustrated by the fact that inherited mutations in Kir channels underlie Type II Bartter’s Syndrome (Kir1.1), Andersen’s Syndrome & Short QT Syndrome (Kir2.1), and certain forms of neonatal diabetes and hyperinsulinaemia (Kir6.2).