Role of the glycoprotein IIb-IIIa complex in plasma membrane Ca2+
transport: a comparison of results obtained with platelets and human
erythroleukemia cells
Z Suldan and LF Brass
Department of Medicine, University of Pennsylvania, Philadelphia 19104.
Several studies have suggested that the glycoprotein (GP) IIb-IIIa complex,
which serves as the platelet fibrinogen receptor, also plays a role in the
regulation of Ca2+ influx across the platelet plasma membrane. To examine
this possibility further, we have compared Ca2+ transport in platelets and
human erythroleukemia (HEL) cells, a megakaryoblastic cell line which
synthesizes GP IIb-IIIa complexes that appear to be identical to those
found on platelets. As with platelets, the results show the presence in
unstimulated HEL cells of a rapidly exchangeable cytosolic Ca2+ pool that
is in equilibrium with an intracellular sequestered Ca2+ pool and with
extracellular Ca2+. Allowing for differences in cell size, the rate
constants for Ca2+ exchange in HEL cells were similar to those in
platelets. As in platelets, thrombin caused an increase in cytosolic Ca2+
that was due partly to enhanced Ca2+ influx and partly to the mobilization
of internal Ca2+ stores. Incubation of the HEL cells with EDTA at 37
degrees C irreversibly altered the GP IIb-IIIa complex as evidenced by
decreased binding of a complex-specific monoclonal antibody. In platelets
this was accompanied by a 40% decrease in the rate of Ca2+ influx. However,
in HEL cells there was neither a diminution in Ca2+ influx nor a reduction
in the magnitude of the increase in cytosolic Ca2+ caused by thrombin.
These results show that the parameters of Ca2+ distribution and movement
are similar in HEL cells and platelets and that in HEL cells, as in
platelets, the GP IIb-IIIa complex can be altered by removing Ca2+.
However, unlike platelets, dissociation of the HEL cell IIb-IIIa complex
has no discernible effect on plasma membrane Ca2+ transport. This suggests
that earlier observations in platelets correlating changes in the rate of
Ca2+ influx with changes in the number of intact IIb-IIIa complexes reflect
an indirect, rather than a direct, role of these proteins in Ca2+
transport.
Volume 78,
Issue 11,
pp. 2887-2893,
12/01/1991
Copyright © 1991 by The American Society of Hematology
