Platelets have been shown to migrate and thus to invade the vascular wall. Platelet migration is stimulated by SDF-1. In other cell types, migration is dependent on Ca(2+) entry via Ca(2+) channels. Ca(2+) influx is sensitive to cell membrane potential which is maintained by K(+) channel activity and/or Cl(-) channel activity. The present study explored the role of ion channels in the regulation of SDF-1 induced migration. Platelets were isolated from human volunteers as well as from gene targeted mice lacking the Ca(2+) activated K(+) channel SK4 (sk4(-/-)) and their wild type littermates (sk4(+/+)). According to confocal microscopy human platelets expressed the Ca(2+) channel Orail and the Ca(2+)-activated K(+) channel K(Ca)3.1 (SK4). SDF-1 (100 ng/ml) stimulated migration in human platelets, an effect blunted by Orail inhibitors 2-aminoethoxydiphenyl borate 2-APB (10 mu M) and SKF-96365 (10 mu M), by unspecific K(+) channel inhibitor TEA (30 mM), by SK4 specific K(+) channel blocker clotrimazole (10 mu M), but not by Cl(-) channel inhibitor 5nitro-2-(3-phenylpropylamino) benzoic acid NPPB (100 mu M). Significant stimulation of migration by SDF-1 was further observed in ske. platelets but was virtually absent in sk(+/+) platelets. In conclusion, platelet migration requires activity of the Ca(2+) channel rail and of the Ca(2+) activated K(+) channel SK4, but not of NPPB-sensitive Cl(-) channels. (C) 2011 Elsevier Inc. All rights reserved.