The Platelet Electrome: Evidence for a Role in Regulation of Function and Surface Interaction

Abstract

Background:

Platelets protect the body from injury through formation of blood clots, changing from a normal, quiescent state to becoming “activated” in response to external stimuli such as chemical cues, shear stress, and temperature. This causes changes in shape, increased adhesion, and alteration of electrical properties such as membrane potential V_m and zeta potential ζ. These electrical phenomena have been regarded as largely unconnected; for example, changes in ζ have been attributed solely to alteration of surface lipid concentration. However, recent reports suggest that cells can alter ζ electrostatically by alteration of V_m in red blood cells. We hypothesized that if platelets also modulate ζ through V_m, this may provide an alternative mechanism to alter cell-cell interaction.

Materials and Methods:

We investigated platelets stored at different temperatures (4°C, 22°C, and 37°C) for 24 h, which is known to alter platelet behavior and electrical properties, and compared these with analyses of freshly harvested platelets. These four conditions exhibited unique sets of electrical properties (V_m, ζ, membrane conductance G_eff, and cytoplasm conductivity σ_cyto), as well as surface exposure of the adhesion molecule P-selectin. These were analyzed to identify correlations between electrical parameters and platelet activation state.

Results:

Many parameters exhibit pairwise correlation across all four conditions, in particular between ζ and G_eff, and between V_m and σ_cyto. Furthermore, when the electrical behavior of platelets stored at 4°C (known to activate the cells) was removed from the analysis, additional relationships were observed among the remaining conditions, including those connecting ζ and V_m to the amount of P-selectin binding.

Conclusion:

Results suggest that V_m may mechanistically alter the availability of cationic molecules at the cell surface, a process never reported before, with implications for our wider understanding of cell-molecule and cell-cell interaction.