Thrombin receptors activate potassium and chloride channels
R Sullivan, DL Kunze and MH Kroll
Research Service, Houston VA Medical Center, TX 77030, USA.
We used DAMI human megakaryocytic leukemia cells to study transmembrane ion
currents activated through the G-protein-coupled thrombin receptor pathway.
When the cells were stimulated by thrombin receptor-activating peptide, an
increase in cytosolic Ca2+ ([Ca2+]i) developed as predicted by the known
effect that thrombin exerts in the platelet. We then monitored the membrane
potentials of individual DAMI cells during this response and observed
complex, triphasic changes that could not be accounted for by Ca2+ fluxes
alone. These consisted of rapid hyperpolarization, followed by
depolarization to values more positive than the resting potential and then
by slow repolarization. For the purpose of this study, we focused on the
hyperpolarizing current that developed immediately after thrombin receptor
activation. This proved to be composed of (1) a Ca(2+)-independent,
outwardly rectifying Cl- current and (2) a strongly hyperpolarizing,
inwardly rectifying, Ba(2+)- sensitive K+ current that required an increase
of [Ca2+]i for activation. By analogy with their functions in other cell
systems, it is logical to conclude that these prominent K+ and Cl-
conductances may serve to regulate the complex volume changes that
accompany thrombin receptor activation and/or to increase the electromotive
drive that supports Ca2+ influx under these conditions through
hyperpolarization of the cell membrane.
Volume 87,
Issue 2,
pp. 648-656,
01/15/1996
Copyright © 1996 by The American Society of Hematology
