Research Overview
Calcium as a Second Messenger in Biology
Calcium is widely used by eukaryotic cells (cells with nuclei) as a second messenger. The function of a second messenger is to provide a link between one kind of signal----such as an electrical signal from the brain to heart muscle----to some kind of cellular event, such as the contraction of the muscle. Specialized equipment, combining microscopic analysis with analysis software, allows these signals to be tracked and analyzed at a cellular level.
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Research Description
Research Area: Physiology
Research Specialties:
calcium channels, calcium sparks, heart failure
Work in the lab focuses on Ca2+ signaling in living cells. By combining confocal, two photon or wide-field microscopy with whole cell patch clamp techniques, we have been able to investigate the effects of subcellular and intracellular Ca2+ concentration ([Ca2+]i on cellular function. Diverse additional tools are used as needed including flash photolysis of caged chemicals, multi-photon uncaging, single channel examination in planar lipid bilayers and by patch clamp, immuno-fluorescence imaging, use of cells from transgenic and gene knockout animals, and use of primary cultures and co-cultures. There are five areas of active work.
Cellular and Molecular Ca2+ Signaling
Local Ca2+ signals depend on the subcellular organization of the affected cells. Ryanodine receptors (RyRs) and IP3 receptors (IP3Rs), intracellular Ca2+ release channels with large conductances that are found in the sarcoplasmic reticulum (SR) and in the endoplasmic reticulum of many cells, are opened...
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Representative Publications
Nelson, M.T., Cheng, H., Rubart, M., Santana, L.F., Bonev, A., Knot, H. & Lederer, W.J. (1995). Relaxation of arterial smooth muscle by calcium sparks. Science 270:633-637.
Gomez, A.M., Valdivia, H.H., Cheng, H., Lederer, M., Santana, L.F., Cannell, M.B., McCune, S.A., Altschuld, R.A. & Lederer, W.J. (1997). Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure. Science 276:800-806.
Santana, L.F., Gomez, A.M. & Lederer, W.J. (1998). Ca2+ flux through promiscuous cardiac Na+ channels: Slip-mode conductance. Science 279:1027-1033.
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