doi: 10.1161/01.RES.0000125883.68447.A1
© 2004 American Heart Association, Inc.
Reviews |
Imaging Microdomain Ca2+ in Muscle Cells
From the Laboratory of Cardiovascular Science (S.-Q.W., D.X.P.B., J.S., L.-S.S., W.W., D.Y., H.C.), National Institute on Aging, NIH, Baltimore, Md; National Laboratory of Biomembrane and Membrane Biotechnology (S.-Q.W., C.W., D.Y.) and The Institute of Molecular Medicine (C.W., H.C.), Peking University, Beijing, China; and the Department of Physiology (G.Z.), The First Military Medical University, Guangzhou, China.
Correspondence to Heping Cheng, PhD, Laboratory of Cardiovascular Science, NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224. E-mail chengp{at}grc.nia.nih.gov
This Review is part of a thematic series on Imaging of Cardiovascular Cells and Tissues, which includes the following articles:
Use of Chimeric Fluorescent Proteins and Fluorescence Resonance Energy Transfer to Monitor Cellular Responses
Imaging Microdomain Ca2+ in Muscle Cells
Optical Imaging of the Heart
Examining Intracellular Organelle Function Using Fluorescent Probes
Two-Photon Microscopy of Cells and Tissues
Brian O’Rourke Guest Editor
Ca2+ ions passing through a single or a cluster of Ca2+-permeable channels create microscopic, short-lived Ca2+ gradients that constitute the building blocks of cellular Ca2+ signaling. Over the last decade, imaging microdomain Ca2+ in muscle cells has unveiled the exquisite spatial and temporal architecture of intracellular Ca2+ dynamics and has reshaped our understanding of Ca2+ signaling mechanisms. Major advances include the visualization of "Ca2+ sparks" as the elementary events of Ca2+ release from the sarcoplasmic reticulum (SR), "Ca2+ sparklets" produced by openings of single Ca2+-permeable channels, miniature Ca2+ transients in single mitochondria ("marks"), and SR luminal Ca2+ depletion transients ("scraps"). As a model system, a cardiac myocyte contains a 3-dimensional grid of 104 spark ignition sites, stochastic activation of which summates into global Ca2+ transients. Tracking intermolecular coupling between single L-type Ca2+ channels and Ca2+ sparks has provided direct evidence validating the local control theory of Ca2+-induced Ca2+ release in the heart. In vascular smooth muscle myocytes, Ca2+ can paradoxically signal both vessel constriction (by global Ca2+ transients) and relaxation (by subsurface Ca2+ sparks). These findings shed new light on the origin of Ca2+ signaling efficiency, specificity, and versatility. In addition, microdomain Ca2+ imaging offers a novel modality that complements electrophysiological approaches in characterizing Ca2+ channels in intact cells.
Key Words: Ca2+ signaling • Ca2+ sparks • Ca2+ channels • excitation-contraction coupling • sarcoplasmic reticulum
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