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a Section of Experimental Anesthesiology, University Clinic Ulm, 89075 Ulm, Germany b Department of Clinical Anesthesiology, University Clinic Ulm, 89075 Ulm, Germany
Key Words: ATP • P2X7 ion channel • inflammatory cytokines • caspase-3 • calcium-activated potassium channel
Address for correspondence: E. Marion Schneider, Ph.D., Sektion Experimentelle Anaesthesiologie, Universitaetsklinikum Ulm, Steinhoevelstrasse 9, 89075 Ulm, Germany. Voice: 0049-0-731-500-60080; fax: 0049-0-731-500-60080. e-mail: marion.schneider{at}uni-ulm.de
Trauma causes immediate cytokine release and the systemic inflammatory response syndrome (SIRS), often preceding sepsis and septic shock. Mechanisms may involve P2X7 ion channel activation via adenosine 5'-triphosphate (ATP) released from surrounding tissue and platelets. A number of single nucleotide polymorphisms (SNPs) influence the nature and magnitude of P2X7-stimulated cytokine release and apoptosis. In whole blood and isolated mononuclear blood cells (PBMCs) of donors with wild-type and heterozygous mutated genotypes, we found downregulated IL-8 and caspase-3 activation but no reproducible effect on tumor necrosis factor (TNF)-
 and IL-1 release. IL-8 and caspase-3 activation were both influenced by paxilline, an inhibitor of calcium-activated potassium channels. Confocal laser scanning microscopy demonstrated that calcium signaling is affected by paxilline as well. We propose that blockade of potassium channels may be relevant to attenuate ATP-induced cytokine responses and apoptosis. The presence of functional SNPs in heterozygous genotypes appears to play a role.
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