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Cardiac Intracellular Ca²⁺ Signaling in Health and Disease
Sponsored by The Association of Latin American Physiological Societies
Cell Signaling Track

Cardiovascular diseases are the most common fatal and disabling disorders in industrialized countries. It is now recognized that alterations in intracellular calcium handling in the cardiac cell  play a critical role in the pathophysiology of most cardiac diseases. Thus, knowledge of calcium movements in the myocyte is crucial for an accurate understanding of cardiac disease at the molecular level and necessary for the development of new therapeutical strategies. Calcium is a universal intracellular regulatory signal involved in the control of a plethora of cellular responses. In the myocardium, intracellular calcium is the central second messenger in the translation of electrical signals (i.e. action potential) into mechanical activity (i.e. contraction). This process -named excitation-contraction coupling (ECC)-  is accomplished through the highly coordinated action of a number of transporters, pumps and ion channels on the cell membrane as well as the sarcoplasmic reticulum (SR), and underlies the calcium fluxes  and  intracellular calcium fluctuations during each cardiac cycle. Alterations of any of these complex mechanisms would obviously constitute a potential trigger for calcium mishandling and cardiac disease. Intracellular calcium not only regulates cardiac contractility but also serves as a ubiquitous second messenger, involved in the control of other signaling  cascades in the cardiac myocyte, key protein kinases and phosphatases, and transcriptional factors. Among these, the calcium–calmodulin–dependent protein kinase II (CaMKII) has emerged in the last few years not only as a central player in maintaining calcium homeostasis in the normal heart, but also as a molecular driver for arrhythmias, apoptosis and cardiac dysfunction. The present symposium will focus on new exciting findings in this central  area of calcium cycling in health and disease. Dr Valdivia and Dr Donoso will describe provocative results on the controversial issue of the role and regulation of SR calcium channels. Whereas Dr Valdivia will describe the role of these channels in  the normal and failing heart  and their possible participation in the production of cardiac arrhtymias,  Dr Donoso will talk about the modulation of these channels by NADPH oxidase and the possible role of this modulation in cardioprotection after an ischemic insult.  Dr Mattiazzi will describe new cascades of events that reveal CaMKII activation as a double-edged sword, both beneficial and detrimental, on the reversible and irreversible ischemia/reperfusion injury, respectively.  Finally, Dr Bers, will present novel aspects of the recently discovered role of CaMKII- dependent mechanisms in excitation-transcription coupling, hypertrophy and heart failure.