Calcium-Dependent Signaling in Cardiac Myocytes

Excerpt

Calcium (Ca) is a key regulator of cardiac function. Through interactions with various molecular binding partners, Ca controls both acute processes, such as ion channel gating and myofilament contraction, and long-term events such as transcriptional changes that regulate myocardial development, growth, and death. Cardiac myocyte Ca levels are modulated by complex networks of signaling mechanisms and precise subcellular structural organization that fine-tune the myocyte response to any given stimulus and allow for rhythmic contraction. On the other hand, disrupted Ca handling and Ca signaling abnormalities are well-established mediators of contractile dysfunction and transmembrane potential instabilities leading to arrhythmia. In this chapter, we discuss the most recent advances in understanding the complexities of Ca signaling in health and widespread cardiac disease, namely, heart failure and arrhythmia. We specifically focus on novel emerging aspects of Ca/calmodulin-dependent protein kinase II signaling and on ultrastructural changes that have been associated with these disease contexts. Unraveling these spatial and temporal aspects of Ca signaling is key to understanding the profound mechanistic consequences of Ca dysregulation for cardiac myocyte and organ function and imperative to inform future therapies that might improve disease outcomes.