Posttranslational modifications of cardiac ryanodine receptors: Ca2+ signaling and EC-coupling

In cardiac muscle, a number of posttranslational protein modifications can alter the function of the Ca(2+) release channel of the sarcoplasmic reticulum (SR), also known as the ryanodine receptor (RyR). During every heartbeat RyRs are activated by the Ca(2+)-induced Ca(2+) release mechanism and contribute a large fraction of the Ca(2+) required for contraction. Some of the posttranslational modifications of the RyR are known to affect its gating and Ca(2+) sensitivity. Presently, research in a number of laboratories is focused on RyR phosphorylation, both by PKA and CaMKII, or on RyR modifications caused by reactive oxygen and nitrogen species (ROS/RNS). Both classes of posttranslational modifications are thought to play important roles in the physiological regulation of channel activity, but are also known to provoke abnormal alterations during various diseases. Only recently it was realized that several types of posttranslational modifications are tightly connected and form synergistic (or antagonistic) feed-back loops resulting in additive and potentially detrimental downstream effects. This review summarizes recent findings on such posttranslational modifications, attempts to bridge molecular with cellular findings, and opens a perspective for future work trying to understand the ramifications of crosstalk in these multiple signaling pathways. Clarifying these complex interactions will be important in the development of novel therapeutic approaches, since this may form the foundation for the implementation of multi-pronged treatment regimes in the future. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

Einzug der Röm. Kays. wie auch der zu Hungarn vnd Böheimb Königl. May. In dero deß H. Reichsstatt Augspurg : den 20. May Anno 1653 ; Was sich von dato, biß auff dero abraiß, wider nach Regenspurg, denckwürdiges begeben vnd sich verloffen

... offeriert vnd dediciert Von Martin Zimmerman, Burger vnd Kunstführer in Augspurg. [Mutmaßl. Stecher: Melchior Küsel]

Aspicis Iliacam, (Qvid Enim Discriminis?) Arcem : Nonne, Vides? Laxat Clavstra Virosqve Sinon ...

Einnahme des Kastells zu Breda, 14. März 1590; mit Textzitaten von H. Grotius

Contrafetische Abbildung Etlicher Alten, Berühmtesten, und Hochgelehrten Herren, die vor- in- und nach der Reformation, mit den Ansehnlichsten Vorgesezten Römischer Kirchen, so wol Schrift- als Mundtlich, vil und grosse Disputationen und Gespräche gehalten, und endtlich durch Gottes Gnad, das Liecht des heiligen Evangelii an tag gegeben haben

42 Reformatoren und Wegbereiter, mit Kürzestviten

Clematis Hendersoni - Waldrebe

AR

[Trillium nivale - Waldlilie]

AR

Orobanche caryophyllacea (auf Galium)

R. Anheisser

[Eryngium alpinum - Alpendistel]

R. Anheisser

[Nymphaea caerulea gigantea - Seerose]

R. Anheisser

[Dictamnus albus (Rutaceae)]

R. Anheisser

[Vanda coerulea (Orchidee)]

AR

Schmarotzer - Orobanche minor - Kleeteufel

R. Anheisser

[Lathraea clandestina - Schuppenwurz]

R. Anheisser

Cypripedium guttatum

AR

Magnolia stellata

AR