Coupled Ca 2+ /H + transport by cytoplasmic buffers regulates local Ca 2+ and H + ion signaling
Open Access
- 15 May 2013
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 110 (22), E2064-E2073
- https://doi.org/10.1073/pnas.1222433110
Abstract
Ca2+ signaling regulates cell function. This is subject to modulation by H+ ions that are universal end-products of metabolism. Due to slow diffusion and common buffers, changes in cytoplasmic [Ca2+] ([Ca2+]i) or [H+] ([H+]i) can become compartmentalized, leading potentially to complex spatial Ca2+/H+ coupling. This was studied by fluorescence imaging of cardiac myocytes. An increase in [H+]i, produced by superfusion of acetate (salt of membrane-permeant weak acid), evoked a [Ca2+]i rise, independent of sarcolemmal Ca2+ influx or release from mitochondria, sarcoplasmic reticulum, or acidic stores. Photolytic H+ uncaging from 2-nitrobenzaldehyde also raised [Ca2+]i, and the yield was reduced following inhibition of glycolysis or mitochondrial respiration. H+ uncaging into buffer mixtures in vitro demonstrated that Ca2+ unloading from proteins, histidyl dipeptides (HDPs; e.g., carnosine), and ATP can underlie the H+-evoked [Ca2+]i rise. Raising [H+]i tonically at one end of a myocyte evoked a local [Ca2+]i rise in the acidic microdomain, which did not dissipate. The result is consistent with uphill Ca2+ transport into the acidic zone via Ca2+/H+ exchange on diffusible HDPs and ATP molecules, energized by the [H+]i gradient. Ca2+ recruitment to a localized acid microdomain was greatly reduced during intracellular Mg2+ overload or by ATP depletion, maneuvers that reduce the Ca2+-carrying capacity of HDPs. Cytoplasmic HDPs and ATP underlie spatial Ca2+/H+ coupling in the cardiac myocyte by providing ion exchange and transport on common buffer sites. Given the abundance of cellular HDPs and ATP, spatial Ca2+/H+ coupling is likely to be of general importance in cell signaling.Keywords
This publication has 45 references indexed in Scilit:
- Cytosolic H+ microdomain developed around AE1 during AE1‐mediated Cl−/HCO3− exchangeJournal Of Physiology-London, 2011
- Determination of the rate of K+ movement through potassium channels in isolated rat heart and liver mitochondriaBiochimica et Biophysica Acta (BBA) - Bioenergetics, 2008
- Calcium SignalingCell, 2007
- pH-Dependence of Extrinsic and Intrinsic H+-Ion Mobility in the Rat Ventricular Myocyte, Investigated Using Flash Photolysis of a Caged-H+ CompoundBiophysical Journal, 2007
- Loading rat heart myocytes with Mg2+ using low‐[Na+] solutionsJournal Of Physiology-London, 2006
- A Buffering SERCA Pump in Models of Calcium DynamicsBiophysical Journal, 2006
- Proton transfer through the membrane—water interfaces in uncoupled mitochondriaBiochemistry (Moscow), 2005
- pH Microdomains in OligodendrocytesOnline Journal of Public Health Informatics, 2004
- Location of the initiation site of calcium transients and sparks in rabbit heart Purkinje cellsJournal Of Physiology-London, 2001
- Analysis of Carnosine, Homocarnosine, and Other Histidyl Derivatives in Rat BrainJournal of Neurochemistry, 1990