Effects of Enhanced P2X₁ Receptor Ca²⁺ Influx on Functional Responses in Human Platelets

Summary

G-protein-coupled P2Y₁ and P2Y₁₂ receptors play key roles in platelet activation, however the importance of ionotropic P2X₁ receptors remains unclear. Platelet P2X₁ responses are highly labile in vitro, but were greatly enhanced by increasing [Ca²+]o in the range 1–10 mM. The P2X₁ agonist α,β-MeATP stimulated a shape change which saturated at peak [Ca²+]_i of ≥ 400 nM, without evidence for aggregation. The maximal P2X₁-evoked transmission decrease was 82% of that obtained via P2Y₁ receptors. α., β-MeATP caused a disc to sphere transformation in virtually all platelets, but lacked the long processes produced by ADP. Following block of P2Y₁ receptors with A3P5PS, co-stimulation with α., β-MeATP and ADP failed to induce aggregation despite the generation of peak [Ca²+]_i responses similar to those stimulated via P2Y1 receptors. Therefore early, transient Ca²⁺ influx via P2X₁ receptors can contribute to platelet activation by stimulating a significant morphological change, but does not readily synergise with P2Y₁₂ receptors to support aggregation.

Keywords

P2X₁ - shape change - aggregation - platelets - P2Y

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