Calcium Signaling in Cardiac Ventricular Myocytes

A bstract : Calcium (Ca) is a multifunctional regulator of diverse cellular functions. In cardiac muscle Ca is a direct central mediator of electrical activation, ion channel gating, and excitation‐contraction (E‐C) coupling that all occur on the millisecond time scale. The key amplification step in E‐C coupling is under tight control of very local [Ca]. Ca also directly activates signaling via kinases and phosphatases (e.g., Ca‐calmodulin‐dependent protein kinase [CaMKII] and calcineurin) that occur over a longer time scale (seconds to minutes), and the co‐localization of these Ca‐dependent modulators to their targets and to Ca is also critical in distinct signaling pathways. Finally, Ca‐dependent signaling is also involved in long‐term (minutes to hours/days) alterations in gene expression (or excitation‐transcription coupling). These pathways are involved in hypertrophy and heart failure, and they can alter the expression of some of the key Ca regulatory proteins involved in E‐C coupling and their regulation by kinases and phosphatases. There may again be physical microenvironments involved in this nuclear transcription, such that they sense a discrete Ca signal that is distinct from that involved in E‐C coupling. In this way cells can use Ca signaling in multiple ways that function in spatially and temporally distinct manners.