Section of Cellular Signaling

Department of Molecular Biophysics & Physiology

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* Former laboratory partner Jingsong Zhou is now at KCUMB


The research group led by Eduardo Ríos is a component of the Section of Cellular Signaling at Rush University.  It focuses on the processes of excitation-coupling in skeletal and cardiac muscle.  Central to them are calcium signaling and the calcium channels that participate in it


Calcium Signaling

    Multicellular organisms coordinate the activity of individual cells through signals that determine metabolic changes.  Inside cells, signals are often transient changes in free [Ca].  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 free [Ca] 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.   

    Here we describe the general  approaches of our research.  To dig deeper, please view: "Tools",  "Key concepts", "Control of Ca inside the SR", "Research update (2015)" and "Artificial Ca sparks".



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 Ca sparks (Cheng et al., 1993), followed in skeletal muscle with our description of sparks: Tsugorka, Ríos & Blatter, 1995.

    While they are local, sparks were soon found to involve multiple intracellular Ca channels.  Studies from our laboratory demonstrated that sparks require a special isoform of the Ca release channel that is not normally present in muscle of adult mammals.  Figueroa et al., 2012.

    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 & Ríos, J. Gen. Physiol., 1997.  The couplon concept was later extended to cardiac muscle.  Stern et al., J. Gen. Physiol., 1999.  In 2013 we revisited the modeling approach in view of recent experimental advances: Stern, Ríos & Maltsev, J. Gen. Physiol., 2013.

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, 2007Royer et al., J. Gen. Physiol., 2010.


Inside the SR

    A recent focus is the development of techniques for imaging calcium inside cellular organelles, especially the sarcoplasmic reticulum (SR).  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 applications of SEER 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 [Ca] inside the sarcoplasmic reticulum.  Sztretye et al., J. Gen. Physiol., 2011, Sztretye et al., J. Gen. Physiol., 2011b.


"SLICs" and CICR

   An advanced dual laser scanner, was used to produce Synthetic Local Increases of Ca in the cytosol (named SLICs), while simultaneously imaging cytosolic calcium concentration.  In this way we could directly probe the sensitivity to calcium of muscle cells, which in some cases allows the production of calcium-induced calcium release (CICR).  Figueroa et al., J. Physiol., 2012.


Contact us

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

Office: 312-942-2081 

Fax: 312-942-8711

E-Mail to:,

Correspondence regarding this web site should be sent to Dr. John Tang:

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