Molecular identity and physiological role of epithelial potassium recycling channels
One of the Kv channel alpha subunits, called KCNQ1, is curious in that it can function as a voltage-gated potassium channel, but is converted to a constitutively active, relatively voltage-independent potassium channel by MiRP1 (KCNE2) or MiRP2 (KCNE3). We are studying the mechanisms by which the single transmembrane domain ancillary subunits MiRP1 and MiRP2 can lock the KCNQ1 S4 voltage sensor in the activated conformation, enabling KCNQ1 to maintain a relatively high open probablity at hyperpolarized potentials.
In addition to mechanisms of channel function, we are studying the physiologic role of KCNQ1-MiRP1 and KCNQ1-MiRP2 channels. One of their functions appears to be to act as potassium 'recycling' pathways, to facilitate efflux of potassium ions that were introduced into the cell by various types of potassium ion co-transporter, depending upon the tissue. One example is in gastric parietal cells, which line gastric glands and secrete gastric acid - important for digestion but also for controlling gut bacteria. As the gastric H /K -ATPase pumps protons into the stomach lumen, potassium ions enter the cell. KCNQ1-MiRP1 channels appera to provide an apical conduit for potassium ion escape from the cell, preventing potassium depletion in the stomach lumen and potassium accumulation in the parietal cell.
Relevant articles
Panaghie, G. & Abbott, G.W. The role of S4 charges in voltage-dependent and voltage-independent KCNQ1 potassium channel complexes. J Gen Physiol. 2007 Feb;129(2):121-33. Epub 2007 Jan 16. PMID: 17227916
Roepke, T.K., Anantharam, A., Kirchhoff, P., Busque, S.M., Young, J.B., Geibel, J.P., Lerner, D.J., & Abbott G.W. The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion. Journal of Biological Chemistry 281 (33): 23740-23747, 2006
