ADP Induced Depolarization of Human Platelet Membrane Potential

The transmembrane potential of human blood platelets suspended in plasma was investigated by studying the distribution of a radiolabeled permeant ion [14C] thiocyanate. The membrane potential of resting platelets was found to be -54.50 mV +/- 9.23 S.D. with a range of -39 to -76 mV (n = 27). The possibility that platelet activation alters membrane potential or that changes in membrane potential serve as an activation trigger was investigated. Stimulation by ADP (10 microM) resulted in a significant (p less than 0.05) depolarization of the membrane potential. Preincubation with 6 mM EGTA failed to inhibit ADP-induced depolarization even though EGTA effectively prevented primary and secondary aggregation but not shape change. Preincubation with PGE1 inhibited shape change, aggregation, and the ADP-induced depolarization. No significant change in membrane potential was observed following stimulation by epinephrine (50 microM). These results suggest that the initial interaction of ADP and its receptor may involve an inward positive current which can be determined by thiocyanate distribution.