Model for the regulation of platelet volume and responsiveness by the trans-membrane Na+/K(+)-pump.
The correspondence between K+ uptake in platelets to their responsiveness was studied using 86Rb+ as an analogue of K+. An average 86Rb+ uptake rate of 0.73 (+/- 0.140) x 10(-15) mole Rb+/min-plt (n = 20) was observed. By the use of K(+)-influx inhibitors, we were able to distinguish three distinct 86Rb+ uptake pathways: an ouabain-sensitive (61% +/- 2% inhibitable) pump and two equivalent channels, only one of which is sensitive to furosemide. Other platelet parameters were also examined in conjunction with K(+)-uptake. Platelets incubated with ouabain exhibited an overall rise in their cell volume (MPV) with incubation time (delta MPV = 7.4 x 10(-17) L/min-1 plt-1). Concomitantly, over 24 hours, a steady decrease in platelet number was recorded by blood cell coulter, which correlated inversely with the counts of particles, which by their size resemble white blood cells (r = 0.89). On a cellular level, incubation with ouabain induced greater expression of surface fibrinogen-receptor (GPIIb), increased binding of FITC-labelled fibrinogen, and increased responsiveness to ADP. Our observations suggest the following sequence of events: Ouabain turns off the Na+/K(+)-ATPase pump, which leads to water accumulation in platelets and concomitant increased MPV. Greater expression of fibrinogen receptors on the distended platelet surface corresponds to spontaneous microaggregate formation as well as greater responsiveness to agonists. Our model links volume regulation, the expression of fibrinogen receptors, and the sensitivity of platelets to agonists to the activity of the Na+/K(+)-ATPase pump.
Marx
G
G
New York Blood Center, NY 10021.
Blankenfeld
A
A
Panet
R
R
Gorodetsky
R
R
D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry; D005665:Furosemide / Q000494:pharmacology; D008954:Models, Biological; D010042:Ouabain / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D012413:Rubidium / Q000493:pharmacokinetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
D010980:Platelet Membrane Glycoproteins; D010042:Ouabain; D005665:Furosemide; D005340:Fibrinogen; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium