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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Recent Publications
Dobrev D, Teos LY,
Lederer WJ. (2008) Unique atrial myocyte
Ca(2+) signaling. Journal of Molecular and Cellular
Cardiology. [Dec 25; Epub ahead of print]
Cheng, H., Lederer,
W.J. (2008) Calcium Sparks.
Physiological Reviews 88,1491–1545.
van Oort ,R.J.,
Altamirano, J., Lederer, W.J., Wehrens, X.H. (2008) Alternative splicing: A key
mechanism for ankyrin-B functional diversity? Journal of Molecular
and Cellular Cardiology. 45, 709-11.
Hund, T.J., Ziman, A.P.,
Lederer, W.J., Mohler, P.J. (2008) The cardiac IP(3) receptor: Uncovering the
role of "the other" calcium-release channel. Journal of Molecular and Cellular
Cardiology 44, 159-61.
Boyman, L., Hiller,
R., Lederer, W.J., Khananshvili, D.
(2008) Direct loading of the purified endogenous inhibitor into the
cytoplasm of patched cardiomyocytes blocks the ion currents and calcium
transport through the NCX1 protein. Biochemistry 47, 6602–6611.
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