© 2001 American Heart Association, Inc.
Cellular Biology |
Coordinated Control of Cell Ca2+ Loading and Triggered Release From the Sarcoplasmic Reticulum Underlies the Rapid Inotropic Response to Increased L-Type Ca2+ Current
From the Unit of Cardiac Physiology, University of Manchester, Manchester, UK.
Correspondence to A.W. Trafford, Unit of Cardiac Physiology, University of Manchester, 1.524 Stopford Bldg, Oxford Rd, Manchester M13 9PT, UK. E-mail trafford{at}man.ac.uk
Abstract—The aim of this study was to investigate how sarcoplasmic reticulum (SR) Ca2+ content and systolic Ca2+ are controlled when Ca2+ entry into the cell is varied. Experiments were performed on voltage-clamped rat and ferret ventricular myocytes loaded with fluo-3 to measure intracellular Ca2+ concentration ([Ca2+]i). Increasing external Ca2+ concentration ([Ca2+]o) from 1 to 2 mmol/L increased the amplitude of the systolic Ca2+ transient with no effect on SR Ca2+ content. This constancy of SR content is shown to result because the larger Ca2+ transient activates a larger Ca2+ efflux from the cell that balances the increased influx. Decreasing [Ca2+]o to 0.2 mmol/L decreased systolic Ca2+ but produced a small increase of SR Ca2+ content. This increase of SR Ca2+ content is due to a decreased release of Ca2+ from the SR resulting in decreased loss of Ca2+ from the cell. An increase of [Ca2+]o has two effects: (1) increasing the fraction of SR Ca2+ content, which is released on depolarization and (2) increasing Ca2+ entry into the cell. The results of this study show that the combination of these effects results in rapid changes in the amplitude of the systolic Ca2+ transient. In support of this, the changes of amplitude of the transient occur more quickly following changes of [Ca2+]o than following refilling of the SR after depletion with caffeine. We conclude that the coordinated control of increased Ca2+ entry and greater fractional release of Ca2+ is an important factor in regulating excitation-contraction coupling.
Key Words: calcium • sarcoplasmic reticulum • trigger
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