Loyola University Chicago, Department of Physiology, Maywood, Illinois 60153, USA
Address for correspondence: Prof. Donald Bers, Ph.D., Department of Physiology, Loyola University Chicago, 2160 S. First Ave, Maywood, IL 60153, USA. Voice: 708-216-1018; fax: 708-216-6308. dbers{at}lumc.edu
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.
