Sarco/endoplasmic reticulum Ca2+-ATPase isoforms: diverse responses to acidosis

Abstract

The effects of acidic pH on the kinetics of Ca2+-ATPase isoforms from intracellular membranes of skeletal muscle, cardiac muscle, cerebellum and blood platelets were studied. At neutral pH, all four Ca2+-ATPase isoforms exhibited similar Ca2+-concentration requirements for half-maximal rates of Ca2+ uptake and ATP hydrolysis. A decrease in the pH from 7.0 to 6.0 promoted a decrease in both the apparent affinity for Ca2+ [increasing half-maximal activation (K0.5)] and the maximal velocity (Vmax) of Ca2+ uptake. With skeletal muscle vesicles these effect were 5 to 10 times smaller than those observed with all the other isoforms. Acidification of the medium from pH 7.0 to 6.5 caused the release of Ca2+ from loaded vesicles and a decrease in the amount of Ca2+ retained by the vesicles at the steady state. With the vesicles derived from skeletal muscle these effects were smaller than for vesicles derived from other tissues. The rate of passive Ca2+ efflux from skeletal and cardiac muscle vesicles, loaded with Ca2+ and diluted in a medium containing none of the ligands of Ca2+-ATPase, was the same at pH 7.0 and 6.0. In contrast, the rate of Ca2+ efflux from cerebellar and platelet vesicles increased 2-fold after acidification of the medium. The effects of DMSO, Mg2+ with Pi and arsenate on the rate of Ca2+ efflux varied among the different preparations tested. The differences became more pronounced when the pH of the medium was decreased from 7.0 to 6.0. It is proposed that the kinetic differences among the Ca2+-ATPase isoforms may reflect different adaptations to cellular acidosis, such as that which occurs during ischaemia.

Mitochondrial Dysfunction in Skeletal Muscle of Amyloid Precursor Protein-overexpressing Mice

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Ex vivo treatment with nitric oxide increases mesoangioblast therapeutic efficacy in muscular dystrophy

“…A good candidate molecule to increase the efficiency of muscle repair by mesoangioblasts is nitric oxide (NO), a shortlived messenger generated by skeletal muscle to play important roles in regulating its own physiological functions (Wolosker et al, 1997;Bredt, 1998;Balon and Nadler, 1997;Stamler and Meissner, 2001;Eu et al, 2003;Shen et al, 1994;Wang et al, 1995;Clementi and Meldolesi, 1997;Nisoli et al, 2004). Several pieces of evidence support this idea.…”

Uncoupling of Ca2+ transport ATPase in muscle and blood platelets by diacylglycerol analogues and cyclosporin A antagonism

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