AJP - Heart and Circulatory Physiology, Vol 249, Issue 6 1211-H1215, Copyright © 1985 by American Physiological Society
Low concentrations of A23187 increase calcium uptake by cardiac sarcoplasmic reticulum
J. J. Murray, A. V. Kuzmin, P. W. Reed and D. O. Levitsky
The divalent cation ionophore A23187 at a concentration of 1 nM produced an
increased rate of oxalate-supported calcium uptake by isolated cardiac
sarcoplasmic reticulum as determined by absorbance changes of the
calcium-sensitive dye murexide. Addition of a higher concentration of
A23187 (0.1 microM) produced a decreased rate of calcium uptake.
Measurement of the time during which ATPase was activated by calcium
addition also suggested an increased rate of calcium uptake in the presence
of 1 nM A23187 and an inhibition of calcium uptake at a higher
concentration of the ionophore (0.1 microM). Ca2+-stimulated ATPase
activity and incorporation of 32Pi from [gamma-32P]ATP into sarcoplasmic
reticular proteins were increased by A23187 at concentrations of 1 nM or
greater. An increased coupling of calcium uptake to ATP hydrolysis was
observed at 1 nM A23187, while concentrations of the ionophore greater than
or equal to 10 nM produced a decreased coupling. Addition of an inhibitor
of cyclic AMP-dependent protein kinase decreased the rate of calcium
uptake, and this inhibition was reversed in a concentration-dependent
manner by 0.01-1 nM A23187. These data suggest that A23187 can activate a
mechanism involving the calcium-dependent phosphorylation of protein that
may regulate the activity of the calcium uptake system of the sarcoplasmic
reticulum. These observations appear to provide an explanation for some of
the contractile effects of A23187 in intact cardiac muscle that suggest
that treatment with the ionophore results in an increased sequestration of
calcium from the cytoplasm.
