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© 2000 American Heart Association, Inc.
MiniReview |
Cardiac Intracellular Calcium Release Channels
Role in Heart Failure
From the Center for Molecular Cardiology, Departments of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY.
Correspondence to Andrew R. Marks, MD, Center for Molecular Cardiology, Box 65, Columbia University College of Physicians & Surgeons, Room 9-401, 630 W 168th St, New York, NY 10032. E-mail arm42@columbia.edu
Key Words: calcium channels • excitation-contraction coupling • heart failure
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Introduction |
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This MiniReview is part of a thematic series on Calcium Cycling in Cardiovascular Cells, which includes the following articles: Ca2+ Release Mechanisms, Ca2+ Sparks, and Local Control of Excitation-Contraction Coupling in Normal Heart Muscle Interaction Between Ca2+ and H+ and Functional Consequences in Vascular Smooth Muscle
Cardiac Intracellular Calcium Release Channels: Role in Heart Failure
Calcium Fluxes Involved in Control of Cardiac Myocyte Contraction
C. William Balke, Guest Editor
Calcium (Ca2+) ions are second messengers in numerous signaling pathways in all cell types.1 In the heart, Ca2+ regulates muscle contraction, electrical signals that determine the cardiac rhythm, and probably plays a role in controlling cell growth.2 In the last decade, elucidation of the molecular structure of the intracellular Ca2+ release channels on the sarcoplasmic reticulum (SR) and endoplasmic reticulum has led to an understanding of how these molecules regulate Ca2+ homeostasis in the heart. Consequently, the role of these channels (ryanodine receptors [RyRs] and inositol 1,4,5-trisphosphate receptors [IP3Rs]) in cardiac pathophysiology is beginning to be understood.
Intracellular Ca2+ release channels form a
unique class of ion channels distinguished on the basis of structure,
size, and function (Figure 1
). RyRs and
IP3Rs have large cytoplasmic domains that are
involved in the regulation of the channel pore located in the carboxy
terminal 10% of the channel sequence. The channels are tetrameric
structures composed of 4 RyR or IP3R subunits.
There are 3 forms of RyRs and 3 forms of IP3Rs
(Table). The RyR subunits are
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