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- Title
Modulation of Ca<sup>2+</sup>-dependent Cl<sup>-</sup> channels by calcineurin in rabbit coronary arterial myocytes.
- Authors
Ledoux, Jonathan; Greenwood, Iain; Villeneuve, Louis R.; Leblanc, Normand
- Abstract
The role of the Ca&sup2+;-dependent phosphatase calcineurin (CAN) in the modulation of Ca&sup2+;-dependent Cl[sup-] channels (Cl[subCa]) 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 Ca&sup2+; was increased. C[subCa] currents (I[subCl(Ca)]) elicited by cell dialysis with fixed intracellular Ca&sup2+; levels up to 500 nM were inhibited by 10 µM cyclosporin A (CsA), a specific inhibitor of CaN, in a voltage-dependent manner, whereas currents evoked by 1 µM Ca&sup2+; were not affected. Inhibition of CaN with CsA also led to a significant reduction in Ca&sup2+; sensitivity of the channel at +50 mV; half-maximal activation increased from 363 ± 16 nM Ca&sup2+; in control to 515 &Plusmn; 40 nM Ca&sup2+; in the presence of CsA. Similar effects were observed on I[subCl(Ca)] when a specific peptide fragment inhibitor of CaN (CaN-AF, 5 µM) was dialysed into the cell via the pipette (500 nM Ca&sup2+;). Application of KN-93 (10 µM), a specific inhibitor of CaMKII, enhanced I[subCl(Ca)] in myocytes dialysed with 1 µM Ca&sup2+; but produced no significant effect on this current when the cells were dialysed with 350 or 500 nM Ca&sup2+;. These results are consistent with the notion that in coronary arterial cells, the activity of Cl[subCa] is enhanced by dephosphorylation of the channel or a closely associated regulatory protein. Moreover the balance of CaN and CaMKII regulating I[subCl(Ca)] is dependent on the level of Ca&sup2+; used to activate I[subCl(Ca)].
- Subjects
CALCIUM channels; RABBITS; PROTEIN kinases; CELLS; MUSCLE cells
- Publication
Journal of Physiology, 2003, Vol 552, Issue 3, p701
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/jphysiol.2003.043836