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| Content Provider | PubMed Central |
|---|---|
| Author | Ledoux, Jonathan Greenwood, Iain Villeneuve, Louis R. Leblanc, Normand |
| Copyright Year | 2003 |
| Abstract | The role of the Ca2+-dependent phosphatase calcineurin (CaN) in the modulation of Ca2+-dependent Cl- channels (ClCa) was studied in freshly isolated rabbit coronary arterial myocytes. Immunocytochemical experiments showed that calmodulin-dependent protein kinase II (CaMKII) and CaN were distributed evenly throughout the cytoplasm of coronary myocytes at rest and translocated to the plasmalemma when intracellular Ca2+ was increased. ClCa currents (I Cl(Ca)) elicited by cell dialysis with fixed intracellular Ca2+ levels up to 500 nm were inhibited by 10 μ m cyclosporin A (CsA), a specific inhibitor of CaN, in a voltage-dependent manner, whereas currents evoked by 1 μ m Ca2+ were not affected. Inhibition of CaN with CsA also led to a significant reduction in Ca2+ sensitivity of the channel at +50 mV; half-maximal activation increased from 363 ± 16 nm Ca2+ in control to 515 ± 40 nm Ca2+ in the presence of CsA. Similar effects were observed on I Cl(Ca) when a specific peptide fragment inhibitor of CaN (CaN-AF, 5 μ m) was dialysed into the cell via the pipette (500 nm Ca2+). Application of KN-93 (10 μ m), a specific inhibitor of CaMKII, enhanced I Cl(Ca) in myocytes dialysed with 1 μ m Ca2+ but produced no significant effect on this current when the cells were dialysed with 350 or 500 nm Ca2+. These results are consistent with the notion that in coronary arterial cells, the activity of ClCa is enhanced by dephosphorylation of the channel or a closely associated regulatory protein. Moreover the balance of CaN and CaMKII regulating I Cl(Ca) is dependent on the level of Ca2+ used to activate I Cl(Ca). |
| Related Links | http://dx.doi.org/10.1113/jphysiol.2003.043836 |
| Ending Page | 714 |
| Page Count | 14 |
| Starting Page | 701 |
| File Format | |
| ISSN | 00223751 |
| e-ISSN | 14697793 |
| Journal | The Journal of Physiology |
| Issue Number | Pt 3 |
| Volume Number | 552 |
| Language | English |
| Publisher | Blackwell Science Inc |
| Publisher Date | 2003-11-01 |
| Access Restriction | Open |
| Rights Holder | Blackwell Science Inc |
| Subject Keyword | Physiology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Sports Science |
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