Physiology of intracellular calcium buffering

Eisner, D., Neher, E., Taschenberger, H. and Smith, G. (2023) Physiology of intracellular calcium buffering. Physiological Reviews, 103(4), pp. 2767-2845. (doi: 10.1152/physrev.00042.2022) (PMID:37326298)

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Abstract

Calcium signaling underlies much of physiology. Almost all the Ca2+ in the cytoplasm is bound to buffers, with typically only ∼1% being freely ionized at resting levels in most cells. Physiological Ca2+ buffers include small molecules and proteins, and experimentally Ca2+ indicators will also buffer calcium. The chemistry of interactions between Ca2+ and buffers determines the extent and speed of Ca2+ binding. The physiological effects of Ca2+ buffers are determined by the kinetics with which they bind Ca2+ and their mobility within the cell. The degree of buffering depends on factors such as the affinity for Ca2+, the Ca2+ concentration, and whether Ca2+ ions bind cooperatively. Buffering affects both the amplitude and time course of cytoplasmic Ca2+ signals as well as changes of Ca2+ concentration in organelles. It can also facilitate Ca2+ diffusion inside the cell. Ca2+ buffering affects synaptic transmission, muscle contraction, Ca2+ transport across epithelia, and the killing of bacteria. Saturation of buffers leads to synaptic facilitation and tetanic contraction in skeletal muscle and may play a role in inotropy in the heart. This review focuses on the link between buffer chemistry and function and how Ca2+ buffering affects normal physiology and the consequences of changes in disease. As well as summarizing what is known, we point out the many areas where further work is required.

Item Type:Articles
Additional Information:D.E. was funded by a British Heart Foundation Chair (CH/2000004/12801) and Grant FS/CRTF/21/24140. E.N.’s andH.T.’s work is supported by the German Research Foundation (DFG),Collaborative Research Center 1286“Quantitative Synaptology.” E.N. acknowledges funding by the DFG under Germany’s Excellence Strategy-EXC 2067/1-390729940. G.S. was funded by British Heart Foundation Grant PG/19/55/34545.
Keywords:Physiology (medical), Molecular Biology, Physiology, General Medicine
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey
Authors: Eisner, D., Neher, E., Taschenberger, H., and Smith, G.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Physiological Reviews
Publisher:American Physiological Society
ISSN:0031-9333
ISSN (Online):1522-1210
Published Online:24 August 2023
Copyright Holders:Copyright: © 2023 The Authors
First Published:First published in Physiological Reviews 103(4): 2767-2845
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
307654Adrenergic modulation of ventricular conduction velocity is a novel modulator of electrical excitability in health and diseaseGodfrey SmithBritish Heart Foundation (BHF)PG/19/55/34545SCMH - Cardiovascular & Metabolic Health