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(Circulation Research. 2003;93:40.)
© 2003 American Heart Association, Inc.

Cellular Biology

Ca²⁺ Scraps

Local Depletions of Free [Ca²⁺] in Cardiac Sarcoplasmic Reticulum During Contractions Leave Substantial Ca²⁺ Reserve

Thomas R. Shannon, Tao Guo, Donald M. Bers

From the Department of Physiology (T.R.S., T.G., D.M.B.), Loyola University Chicago, Maywood, Ill; Department of Molecular Biophysics and Physiology (T.R.S.), Rush University, Chicago, Ill.

Correspondence to Thomas R. Shannon, DVM, PhD, Department of Molecular Biophysics and Physiology, Rush University, 1750 W Harrison, Chicago, IL 60612. E-mail tshannon{at}rush.edu

Free [Ca²⁺] inside the sarcoplasmic reticulum ([Ca²⁺]_SR) is difficult to measure yet critically important in controlling many cellular systems. In cardiac myocytes, [Ca²⁺]_SR regulates cardiac contractility. We directly measure [Ca²⁺]_SR in intact cardiac myocytes dynamically and quantitatively during beats, with high spatial resolution. Diastolic [Ca²⁺]_SR (1 to 1.5 mmol/L) is only partially depleted (24% to 63%) during contraction. There is little temporal delay in the decline in [Ca²⁺]_SR at release junctions and between junctions, indicating rapid internal diffusion. The incomplete local Ca²⁺ release shows that the inherently positive feedback of Ca²⁺-induced Ca²⁺ release terminates, despite a large residual driving force. These findings place stringent novel constraints on how excitation-contraction coupling works in heart and also reveal a Ca²⁺ store reserve that could in principle be a therapeutic target to enhance cardiac function in heart failure.

Key Words: calcium homeostasis • sarcoplasmic reticulum • ryanodine receptors • confocal imaging • membrane transport

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