Ca2+ scraps: local depletions of free [Ca2+] in cardiac sarcoplasmic reticulum during contractions leave substantial Ca2+ reserve.
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.
Shannon
Thomas R
TR
Department of Physiology, Loyola University Chicago, Maywood, Ill, USA. tshannon@rush.edu
Guo
Tao
T
Bers
Donald M
DM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D002110:Caffeine; D007545:Isoproterenol; D002118:Calcium