Cation gradient dependence of the steps in thrombin stimulation of human platelets.
Thrombin causes a dose-dependent depolarization of the transmembrane potential of normal human platelets which can be continuously measured by the fluorescent probe, 3,3'-dipropylthiodicarbocyanine, whose distribution across the plasma membrane has been shown to be dependent upon the membrane potential. The dose-dependent depolarization of the platelet's negative membrane potential by thrombin is in large part due to a rapid uptake of sodium. Both the membrane potential change and the rapid sodium influx can be inhibited by a fast acting analog of amiloride, a sodium channel blocker, while valinomycin, a potassium ionophore, has no effect on the potential change nor on the sodium uptake, suggesting that the transmembrane potassium gradient is not important in the thrombin-induced depolarization. Neither the secretion of serotonin nor that of lysosomal enzymes nor the secondary release of the fluorescent probe which correlates with the lysosomal enzyme secretion occur if treatment with valinomycin precedes activation by thrombin. It is thus apparent that: 1) the change in the membrane potential induced by thrombin is directly dependent upon the transmembrane sodium gradient and is primarily due to a dose-dependent sodium uptake by the platelets; and 2) the thrombin-induced secretory processes are dependent upon maintenance of the transmembrane potassium gradients.
D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002794:Choline / Q000494:pharmacology; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials; D010974:Platelet Aggregation; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000097:blood; D013917:Thrombin / Q000502:physiology*; D014634:Valinomycin / Q000494:pharmacology
D014634:Valinomycin; D012701:Serotonin; D005966:Glucuronidase; D013917:Thrombin; D002794:Choline; D011188:Potassium