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.
RESEARCH INTERESTS
Membrane transport mechanisms
Lipid Signaling
Electrophysiology
Calcium Signaling
RECENT PUBLICATIONS
Hilgemann DW, "New insights into the molecular and cellular workings of the cardiac Na+/Ca2+ exchanger." Am J Physiol Cell Physiol, 287(5):C1167-72, November 2004
Horowitz LF, Hirdes W, Suh BC, Hilgemann DW, Mackie K, Hille B, "Phospholipase C in living cells: activation, inhibition, Ca2+ requirement, and regulation of M current." J Gen Physiol, 126(3):243-62, September 2005
Li Y, Gamper N, Hilgemann DW, Shapiro MS, "Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate." J Neurosci, 25(43):9825-35, October 2005
Hilgemann DW, Yaradanakul A, Wang Y, Fuster D, "Molecular control of cardiac sodium homeostasis in health and disease." J Cardiovasc Electrophysiol, 17 Suppl 1:S47-S56, May 2006
Zaika O, Lara LS, Gamper N, Hilgemann DW, Jaffe DB, Shapiro MS, "Angiotensin II regulates neuronal excitability via phosphatidylinositol 4,5-bisphosphate-dependent modulation of Kv7 (M-type) K+ channels." J Physiol, 575(Pt 1):49-67, August 2006
SIGNIFICANT PUBLICATIONS
Hilgemann DW, Lu C-C, "Giant membrane Patches: Improvements and Applications" Methods in Enzymology, 293:267-80, 1998
Hilgemann DW, "Cytoplasmic ATP-dependent regulation of ion transporters and channels: Mechanisms and Messengers" Ann Rev Physiol, 59:193-220, 1997
Hilgemann DW, Ball R, "Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2" Science, 273(5277):956-9, 1996
Hilgemann DW, Feng S, Nasuhoglu C, "The complex and intriguing lives of PIP2 with ion channels and transporters" Sci STKE, 2001(111):RE19, December 2001
Hwang C, Feng Y, and Hilgemann DW, "Direct Interaction of PIP2 with inward rectifier potassium channels and its enhancement by G-beta-gamma" Nature, 391:803-06, 1998
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