Affiliation:
1. 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.
Abstract
Abstract
The [Ca
2+
]
i
transient in heart is now thought to involve the recruitment and summation of discrete and independent “units” of Ca
2+
release (Ca
2+
“sparks”) from the sarcoplasmic reticulum, each of which is controlled locally by single coassociated L-type Ca
2+
channels (“local control theory of excitation-contraction coupling”). All prior studies on Ca
2+
sparks, however, have been performed in single enzymatically dissociated heart cells under nonphysiological conditions. In order to understand the possible significance of Ca
2+
sparks to normal working cardiac muscle, we used confocal microscopy to record Ca
2+
sparks, which are spatially averaged [Ca
2+
]
i
transients (and Ca
2+
waves), in individual cells of intact rat right ventricular trabeculae (composed of <15 cells in cross section) microinjected with the Ca
2+
indicator fluo 3 under physiological conditions ([Ca
2+
]
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 [Ca
2+
]
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 Ca
2+
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 Ca
2+
sparks was ≈170 nmol/L. Ca
2+
sparks occurred at a frequency of 12.0±0.8/s (mean±SEM) in line scans covering 94 sarcomeres. Ca
2+
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 Ca
2+
wave propagation was 3.9±0.3 sarcomere lengths (sarcomere length, 2.2 μm). Ca
2+
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) Ca
2+
sparks, similar to those recorded in single cells, occur in trabeculae under physiological conditions and (2) coupling of Ca
2+
spark generation between neighboring sites occurs and may lead to (3) the development of Ca
2+
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
113 articles.
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