دورية أكاديمية
Irregular spiking in free calcium concentration in single, human platelets. Regulation by modulation of the inositol trisphosphate receptors.
| العنوان: | Irregular spiking in free calcium concentration in single, human platelets. Regulation by modulation of the inositol trisphosphate receptors. |
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| المؤلفون: | van Gorp RM; Department of Biochemistry, University of Maastricht, the Netherlands., Feijge MA, Vuist WM, Rook MB, Heemskerk JW |
| المصدر: | European journal of biochemistry [Eur J Biochem] 2002 Mar; Vol. 269 (5), pp. 1543-52. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 0107600 Publication Model: Print Cited Medium: Print ISSN: 0014-2956 (Print) Linking ISSN: 00142956 NLM ISO Abbreviation: Eur J Biochem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: -2004: Oxford, UK : Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Original Publication: Berlin, New York, Springer. |
| مواضيع طبية MeSH: | Blood Platelets/*metabolism , Calcium/*metabolism , Calcium Channels/*physiology , Receptors, Cytoplasmic and Nuclear/*physiology, Alprostadil/pharmacology ; Cyclic AMP/biosynthesis ; Humans ; Inositol 1,4,5-Trisphosphate/biosynthesis ; Inositol 1,4,5-Trisphosphate Receptors ; Thimerosal/pharmacology |
| مستخلص: | Fluorescence ratio imaging indicates that immobilized, aspirin-treated platelets, loaded with Fura-2, respond to inositol 1,4,5-trisphosphate- (InsP3)-generating agonists such as thrombin by high-frequency, irregular rises in cytosolic [Ca2+]i with spikes that vary in peak level and peak-to-peak interval. This differs from the regular [Ca2+]i oscillations observed in other, larger cells. We found that the thiol-reactive compounds thimerosal (10 microm) and U73122 (10 microm) evoked similar irregular Ca2+ responses in platelets, but in this case in the absence of InsP3 generation. Thrombin-induced spiking was acutely abolished by inhibiting phospholipase C or elevating intracellular cAMP levels, while spiking with sulfhydryl reagents was only partially blocked by cAMP elevation. Confocal laser scanning microscopy using fluo-3-loaded platelets indicated that, with all agonists or conditions, the irregular spikes were almost instantaneously raised in various regions within a single platelet. When using saponin-permeabilized platelets, we found that InsP3-induced Ca2+ release from stores was stimulated by modest Ca2+ concentrations, pointing to a mechanism of InsP3-dependent Ca2+-induced Ca2+ release (CICR). This process was completely inhibitable by heparin. The Ca2+ release by InsP3, but not the CICR sensor, was negatively regulated by cAMP elevation. Thimerosal treatment did not release Ca2+ from intracellular stores, but markedly potentiated the stimulatory effect of InsP3. In contrast, U73122 caused a heparin/cAMP-insensitive Ca2+ leak from stores that differed from those used by InsP3. Taken together, these results demonstrate that InsP3 receptor channels play a crucial role in the irregular, spiking Ca2+ signal of intact platelets, even when induced by agents such as thimerosal or U73122 which do not stimulate InsP3 formation. The irregular Ca2+ release events appear to be subjected to extensive regulation by: (a) InsP3 level, (b) the potentiating effect of elevated Ca2+ on InsP3 action via CICR, (c) InsP3 channel sensitization by sulfhydryl (thimerosal) modification, (d) InsP3 channel-independent Ca2+ leak with U73122, and (e) down-regulation via cAMP elevation. The observation that individual Ca2+ peaks were generated in various parts of a platelet at similar intervals and amplitudes points to effective cooperation of the various stores in the Ca2+-release process. |
| المشرفين على المادة: | 0 (Calcium Channels) 0 (ITPR1 protein, human) 0 (Inositol 1,4,5-Trisphosphate Receptors) 0 (Receptors, Cytoplasmic and Nuclear) 2225PI3MOV (Thimerosal) 85166-31-0 (Inositol 1,4,5-Trisphosphate) E0399OZS9N (Cyclic AMP) F5TD010360 (Alprostadil) SY7Q814VUP (Calcium) |
| تواريخ الأحداث: | Date Created: 20020305 Date Completed: 20020719 Latest Revision: 20190620 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1046/j.1432-1033.2002.02806.x |
| PMID: | 11874470 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0014-2956 |
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| DOI: | 10.1046/j.1432-1033.2002.02806.x |