Imaging microdomain Ca2+ in muscle cells.
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.
Wang
Shi-Qiang
SQ
Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, Md 21224, USA.
Wei
Chaoliang
C
Zhao
Guiling
G
Brochet
Didier X P
DX
Shen
Jianxin
J
Song
Long-Sheng
LS
Wang
Wang
W
Yang
Dongmei
D
Cheng
Heping
H
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000032:analysis*; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D006224:Cricetinae; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating; D017136:Ion Transport; D018613:Microscopy, Confocal / Q000379:methods*; D008929:Mitochondria, Heart / Q000737:chemistry / Q000648:ultrastructure; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology; D032383:Myocytes, Cardiac / Q000737:chemistry* / Q000648:ultrastructure; D032389:Myocytes, Smooth Muscle / Q000737:chemistry* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D011817:Rabbits; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000648:ultrastructure
D020746:Calcium Channels, L-Type; D002614:Chelating Agents; D019837:Ryanodine Receptor Calcium Release Channel; D004533:Egtazic Acid; D002118:Calcium