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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Peng, HongLi Yaney, Gordon C. Kirber, Michael T. |
| Description | Country affiliation: China Author Affiliation: Peng H ( Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.) |
| Abstract | The role of protein kinase C (PKC) in $Ca^{2+}$ release through ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) of vascular smooth muscle cells (SMCs) is not well understood. Caffeine was used to activate RyRs and the intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_{i})$ was measured in both freshly isolated and cultured mouse aortic SMCs (ASMCs). Pre-activation of PKC with 1,2-dioctanoyl-sn-glycerol (DOG) prevented caffeine-induced $[Ca^{2+}]_{i}$ transients. Application of the PKC inhibitor calphostin C caused $[Ca^{2+}]_{i}$ transients which were not blocked by nifedipine or by removing extracellular $Ca^{2+}$ but were abolished after inhibition of the SR $Ca^{2+}–ATPase$ with thapsigargin or after inhibition of RyRs with ryanodine. In addition, chelerythrine and GF109203X also elevated resting $[Ca^{2+}]_{i}$ but no further $[Ca^{2+}]_{i}$ increase was seen with subsequent application of caffeine. Selective inhibition of PKCα with safingol blocked caffeine-induced $[Ca^{2+}]_{i}$ transients, but the PKCε inhibitory peptide V1-2 did not. In cells expressing a EGFP-tagged PKCα, caffeine-induced $[Ca^{2+}]_{i}$ transients were associated with a rapid focal translocation near the cell periphery, while application of ionomycin and DOG caused translocation to the plasma membrane. Western blot showed that caffeine increased the relative amount of PKCα in the particulate fraction in a time-dependent manner. Co-immunoprecipitation of RyRs and PKCα indicated that they interact. In conclusion, our studies suggest that PKC activation can inhibit the gating activity of RyRs in the SR of ASMCs, and this regulation is most likely mediated by the $Ca^{2+}-dependent$ PKCα isoform. |
| File Format | HTM / HTML |
| ISSN | 00316768 |
| Issue Number | 4 |
| Volume Number | 460 |
| e-ISSN | 14322013 |
| Journal | Pflügers Archiv - European Journal of Physiology |
| Language | English |
| Publisher | Springer |
| Publisher Date | 2010-09-01 |
| Publisher Place | Germany |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Physiology Calcium Metabolism Enzyme Activation Physiology Muscle, Smooth, Vascular Protein Kinase C-alpha Ryanodine Receptor Calcium Release Channel Animals Blotting, Western Caffeine Pharmacology Drug Effects Enzyme Inhibitors Immunoprecipitation Mice Protein Transport Journal Article Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) Clinical Biochemistry |
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