Thrombin and NaF, but not epinephrine, raise cytosolic free Na+ in human platelets.

We have investigated changes in [Na+]i in SBFI-loaded platelets stimulated at 37 degrees C with thrombin, epinephrine, and NaF. Basal [Na+]i was 4.9 +/- 1.3 mM (n = 70). Stimulation of platelets with thrombin (0.1 U/ml) in the presence of 1 mM extracellular Ca2+ rapidly raised [Na+]i by 27.3 +/- 6 mM (n = 16). Part of this increase (approx. 20-30%) is caused by Na+/H+ exchange, the rest is predominantly due to Na+ influx. Epinephrine (20 microM) failed to change [Na+]i both in the absence and presence of fibrinogen. This is in agreement with earlier reports showing that epinephrine also fails to activate Na+/H+ exchange in human platelets. NaF which activates platelets via a direct effect on GTP-binding proteins induced a slow rise in [Na+]i to 9.5 +/- 2.5 mM (n = 4) and 33.0 +/- 3.6 mM (n = 12) at 10 and 20 mM NaF, respectively. This effect was completely blocked by SK&F 96365, a blocker of receptor-mediated Ca2+ entry. Hence, the NaF-induced increase in [Na+]i is exclusively due to the opening of non-selective cation channels. This latter finding agrees with earlier observations which showed that NaF does not induce activation of Na+/H+ exchange in platelets.