title: Ion channels in the regulation of platelet migration.
abstract: 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 Orai1 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 Orai1 inhibitors 2-aminoethoxydiphenyl borate 2-APB (10 μM) and SKF-96365 (10 μM), by unspecific K(+) channel inhibitor TEA (30 mM), by SK4 specific K(+) channel blocker clotrimazole (10 μM), but not by Cl(-) channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid NPPB (100 μM). Significant stimulation of migration by SDF-1 was further observed in sk4(+/+) platelets but was virtually absent in sk4(-/-) platelets. In conclusion, platelet migration requires activity of the Ca(2+) channel Orai1 and of the Ca(2+) activated K(+) channel SK4, but not of NPPB-sensitive Cl(-) channels.
authors: Department of Physiology, University of Tübingen, Germany.
authors: Eva-Maria
authors: EM
authors: Schmidt
authors: Patrick
authors: P
authors: Münzer
authors: Oliver
authors: O
authors: Borst
authors: Bjoern F
authors: BF
authors: Kraemer
authors: Evi
authors: E
authors: Schmid
authors: Benjamin
authors: B
authors: Urban
authors: Stephan
authors: S
authors: Lindemann
authors: Peter
authors: P
authors: Ruth
authors: Meinrad
authors: M
authors: Gawaz
authors: Florian
authors: F
authors: Lang
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D009579:Nitrobenzoates / Q000494:pharmacology; D000071740:ORAI1 Protein
chemical_list: D015220:Calcium Channels; D054377:Chemokine CXCL12; D018118:Chloride Channels; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D007473:Ion Channels; C496923:KCNN4 protein, human; D009579:Nitrobenzoates; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid