Circulation Research. 2003;93:40-45
Published online before print June 5, 2003, doi: 10.1161/01.RES.0000079967.11815.19
Published online before print June 5, 2003, doi: 10.1161/01.RES.0000079967.11815.19
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© 2003 American Heart Association, Inc.
Cellular Biology |
Ca2+ Scraps
Local Depletions of Free [Ca2+] in Cardiac Sarcoplasmic Reticulum During Contractions Leave Substantial Ca2+ Reserve
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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