The research groups led by Eduardo Ríos and Jingsong Zhou, components of the Section of Cellular Signaling at Rush University,
focus on calcium signaling, the function of calcium channels, and their role in excitation-coupling in skeletal and cardiac
The research groups led by Eduardo Ríos and Jingsong Zhou, components of the Section of Cellular Signaling at Rush University, focus on calcium signaling, the function of calcium channels, and their role in excitation-coupling in skeletal and cardiac muscle.
Multicellular organisms coordinate the activity of individual cells through signals that determine metabolic changes. Inside cells, signals are often transient changes in [Ca2+]. We study these changes and try to understand their mechanisms and roles within healthy cells, as well as their alterations in a number of diseases.
Calcium signals are ubiquitous and crucial. Excitation-contraction (E-C) coupling, the process that translates muscle membrane depolarization to increase in intracellular [Ca2+] and contraction, is the first recognized example of Ca signaling. Our group tries to understand E-C coupling at the molecular and cellular levels. These questions transcend muscle physiology, given the widespread distribution of Ca signaling in other types of muscle, nerve cells and other tissues. Currently there is agreement on the basic aspects and mechanisms of signaling in healthy cells. We are now trying to clarify function in altered conditions, chiefly fatigue and disease.
are cellular and molecular.
Cellular methods include recording of calcium changes "globally" (that is, averaged over the whole cell) or locally, which is done by confocal microscopic imaging. The study of local events started in cardiac muscle with the discovery of Ca2+ sparks (Cheng et al. 1993), followed in skeletal muscle with our description of sparks: Tsugorka, Ríos and Blatter.1995.
While they are local, sparks were soon found to involve multiple intracellular Ca channels. Example studies from our group: Brum et al. 2000. Launikonis et al. PNAS USA. 2006. Ríos et al. J Gen Physiol. 2008.
The local studies are carried out in parallel with recording of global or "whole cell" signals. An early exampl : Shirokova, N., García, J., Pizarro, G. and Ríos, E. J. Gen. Physiol, 1996.
The definition of processes and mechanisms is often achieved through formal quantitative modeling. In 1997 we introduced the "couplon" as the functionally relevant multi-channel unit: Stern, Pizarro and Ríos. J. Gen. Physiol. 1997. The couplon concept was later extended to cardiac muscle. Stern et al. .1999. In 2013 we revisited the modeling approach in view of recent experimental advances: Stern, Ríos & Maltsev; J Gen Physiol 2013
Newer examples of work at the global level include The cell boundary theorem. A simple law of the control of calcium concentration. Rios, J. Physiol. Sci. 2010 and Evolution and modulation of intracellular calcium release during long-lasting, depleting depolarization in mouse muscle. Royer L, Pouvreau S, Ríos E. J Physiol. 2008
Molecular approaches include modifying the endowment of native proteins, or adding foreign ones, to then explore the functional consequences of these changes. Examples: Pouvreau et al. PNAS USA, 2007. Royer et al J Gen Physiol. 2010
Inside the SR
A recent focus is the development of techniques for imaging calcium inside cellular organelles. An early success was the development of the SEER technique. Launikonis et al. J Physiol, 2005. In 2013 the same technique was used to improve imaging of membrane voltage: Manno et al. J Gen Physiol 2013 For other developments see "Control of Ca inside the SR" .
A major advance in this direction was the development of a novel biosensor, the fusion of the cameleon D4cpv and the intra-SR protein calsequestrin, to image [Ca2+] inside the sarcoplasmic reticulum. et al. . 2011.
"SLICs" and CICR
An advanced dual laser scanner, was used to produce artificial Ca sparks in the cytosol of a cell, while simultaneously imaging its cytosolic calcium concentration. In this way we could directly probe the sensitivity to calcium of muscle cells. Figueroa et al J. Physiol. 2012.
Ms. Lucille Vaughn, Dept. Molecular Biophysics and Physiology
Section of Cellular Signaling, Rush University School of Medicine
1750 W. Harrison St. Suite 1279JS, Chicago, IL 60612, USA
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