© 1997 American Heart Association, Inc.
Articles |
Ca2+ `Sparks' and Waves in Intact Ventricular Muscle Resolved by Confocal Imaging
From the Department of Physiology (W.G.W., C.W.B.) and the Division of Cardiology, Department of Medicine (C.W.B.), University of Maryland School of Medicine, Baltimore; the Departments of Medicine, Physiology, and Biophysics (H.E.D.J. ter K.), The University of Calgary (Canada); and the Division of Cardiology, Department of Medicine (E.M., W.D.G.), The Johns Hopkins University School of Medicine, Baltimore, Md.
Correspondence to Dr W.G. Wier or Dr C.W. Balke, Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore St, Baltimore, MD 21201. E-mail gwier001@umabnet.ab.umd.edu or bbalke{at}heart.ab.umd.edu
Abstract The [Ca2+]i transient in
heart is now thought to involve the recruitment and summation of
discrete and independent "units" of Ca2+ release
(Ca2+ "sparks") from the sarcoplasmic reticulum, each
of which is controlled locally by single coassociated L-type
Ca2+ channels ("local control theory of
excitation-contraction coupling"). All prior studies on
Ca2+ sparks, however, have been performed in single
enzymatically dissociated heart cells under
nonphysiological conditions. In order to understand
the possible significance of Ca2+ sparks to normal working
cardiac muscle, we used confocal microscopy to record
Ca2+ sparks, which are spatially averaged
[Ca2+]i transients (and Ca2+
waves), in individual cells of intact rat right ventricular
trabeculae (composed of <15 cells in cross section)
microinjected with the Ca2+ indicator fluo 3 under
physiological conditions
([Ca2+]o, 1 mmol/L; temperature,
33±1°C). Twitch force was recorded simultaneously.
When stretched to optimal length (sarcomere length, 2.2 µm) and
stimulated at 0.2 Hz, the trabeculae generated 
700 µg
of force per cell. Spatially averaged [Ca2+]i
transients recorded from individual cells within a
trabecula were similar to those recorded previously
from single cells. The amplitude distribution of the peak ratio of
Ca2+ sparks was bimodal, with maxima at ratios of 1.8±0.3
and 2.7±0.2 (mean±SD), respectively. The amplitude of the peak of
Ca2+ sparks was 170 nmol/L. Ca2+ sparks
occurred at a frequency of 12.0±0.8/s (mean±SEM) in line scans
covering 94 sarcomeres. Ca2+ waves occurred randomly at a
frequency of 0.57±0.08/s and propagated with a velocity of
29.5±1.7 µm/s. The extent of Ca2+ wave propagation
was 3.9±0.3 sarcomere lengths (sarcomere length, 2.2 µm).
Ca2+ sparks could be identified along the leading edge of
the waves at intervals of 1.30±0.11 sarcomere length. Our observations
suggest that (1) Ca2+ sparks, similar to those recorded
in single cells, occur in trabeculae under
physiological conditions and (2) coupling of
Ca2+ spark generation between neighboring sites occurs and
may lead to (3) the development of Ca2+ waves, which
propagate under physiological conditions at a low
velocity over limited distances. The results suggest that concepts of
excitation-contraction coupling recently derived from isolated myocytes
are applicable to intact cardiac trabeculae.
Key Words: heart • excitation-contraction coupling • trabeculae • Ca2+ spark • Ca2+ wave
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