Effect of Casein Kinase 1a Activator Pyrvinium Pamoate on Erythrocyte Ion Channels
| Autor: | Matthias Eberhard, Syed M. Qadri, Florian Lang, Christine Zelenak, Yuliya Kucherenko |
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| Rok vydání: | 2012 |
| Předmět: |
Erythrocytes
Patch-Clamp Techniques Physiology Ion Channels Cell membrane Potassium Channels Calcium-Activated Pyrvinium Compounds chemistry.chemical_compound Cations medicine Humans Patch clamp Annexin A5 Protein kinase A Ion channel Cell Size Aniline Compounds Ionomycin Cell Membrane Casein Kinase Ialpha Phosphatidylserine Molecular biology Electrophysiological Phenomena Cytosol medicine.anatomical_structure Xanthenes chemistry Biophysics Calcium Casein kinase 1 Protein Binding |
| Zdroj: | Cellular Physiology and Biochemistry. 30:407-417 |
| ISSN: | 1421-9778 1015-8987 |
| DOI: | 10.1159/000339034 |
| Popis: | Pharmacological modification of protein kinase CK1 (casein kinase 1) has previously been shown to influence suicidal erythrocyte death or eryptosis, which is triggered by activation of Cl(-)-sensitive Ca(2+)-permeable cation channels. Ca(2+) entering through those channels stimulates cell membrane scrambling and opens Ca(2+)-activated K(+)-channels resulting in KCl exit and thus cell shrinkage. The specific CK1-inhibitor D4476 (1 µM) blunted, whereas the specific CK1 αactivator pyrvinium pamoate (10 µM) enhanced cell membrane scrambling. The substances were at least partially effective through modification of cytosolic Ca(2+)-activity. The present study explored, whether pyrvinium pamoate indeed influences Cl(-)-sensitive cation-channels in erythrocytes. As a result, removal of Cl(-)increased Fluo3-fluorescence (reflecting cytosolic Ca(2+)-activity), triggered cell membrane scrambling (apparent from annexin-V-binding), and decreased forward scatter (pointing to cell shrinkage). Pyrvinium pamoate significantly augmented the effect of Cl(-)-removal on Fluo3 fluorescence and annexin-V-binding, but blunted the effect on forward scatter. According to whole cell patch clamp recording, Cl(-)removal activated a cation current, which was significantly enhanced by pyrvinium pamoate. Pyrvinium pamoate inhibited Ca(2+)-activated K(+)-channels. Ca(2+)-ionophore ionomycin (1 µM) decreased forward scatter, an effect significantly blunted by pyrvinium pamoate. In conclusion, pyrvinium pamoate activates Cl(-)-sensitive Ca(2+)-permeable cation channels with subsequent Ca(2+)-entry and inhibits Ca(2+)-activated K(+)-channels thus blunting the stimulating effect of Ca(2+) on those channels, K(+)-exit and thus cell shrinkage. |
| Databáze: | OpenAIRE |
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