We study ion channels and transporters that regulate a wide range of cell functions, from cardiac contraction to vision to secretion. The transporters include a cardiac Na/Ca exchange system, the Na/K pump, and sodium-coupled neurotransmitter transporters. The ion channels include potassium channels, which control the rates of electrical activity in tissues from brain to heart to pancreas, and they include ion channels which are opened by cyclic nucleotides and whose activity initiates the vision and smell processes. To improve biophysical and regulatory studies of these mechanisms, we improved the so-called 'patch clamp' electrophysiological methods to allow us to excise 'giant' membrane patches from many cell types. Our methods allow us to study conformational changes of transport proteins with one microsecond resolution, and it is our long-term goal to reconstitute important membrane-associated processes in the patches such as phototransduction, calcium release, and membrane insertion and retrieval. Recently, we discovered that phosphatidylinositides are important regulators of a wide range of ion transporters and channels. We are now studying how enzymes involved in phosphatidylinositide synthesis and degradation are regulated by cell signaling mechanisms, and how ultimately they regulate cell function through modulation of ion transport activities.
Lu, C and DW Hilgemann (1999) GAT1 (GABA:Na:Cl) cotranpsort function. [3 articles] Journal of General Physiology 114:427-475.
Huang, CL, S Feng and DW Hilgemann (1998) Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by G-beta-gamma. Nature 391:803-806.
Hilgemann, DW and R Ball (1996) Regulation of cardiac Na , Ca2 exchange and KATP potassium channels by PIP2. Science 273:956-9.
Hilgemann, DW (1996) Unitary cardiac Na , Ca2 exchange current magnitudes determined from channel-like noise and charge movements of ion transport. Biophys J 71:759-68.