| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received March 26, 2003
Revised May 1, 2003
Accepted after revision August 18, 2003
1 University of Montreal
2 St. George's Hospital Medical School
3 Montreal Heart Institute
4 University of Nevada School of Medicine
* To whom correspondence should be addressed. E-mail: nleblanc{at}med.unr.edu.
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 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 (ICl(Ca) ) elicited by cell dialysis with fixed intracellular Ca2+ levels up to 500 nM were inhibited by 10 µM cyclosporin A (CsA) in a voltage- dependent manner, a specific inhibitor of CaN, whereas currents evoked by 1 µM 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 ICl(Ca) when a specific peptide fragment inhibitor of CaN (CaN-AF, 5 µM) was dialysed into the cell via the pipette (500 nM Ca2+). Application of KN-93 (10 µM), a specific inhibitor of CaMKII, enhanced ICl(Ca) in myocytes dialysed with 1 µM 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 ICl(Ca) is dependent on the level of Ca2+ used to activate ICl(Ca) .
This article has been cited by other articles:
|
|
 |
|
  V. V. Matchkov, P. Larsen, E. V. Bouzinova, A. Rojek, D. M. B. Boedtkjer, V. Golubinskaya, F. S. Pedersen, C. Aalkjaer, and H. Nilsson Bestrophin-3 (Vitelliform Macular Dystrophy 2-Like 3 Protein) Is Essential for the cGMP-Dependent Calcium-Activated Chloride Conductance in Vascular Smooth Muscle Cells Circ. Res., October 10, 2008; 103(8): 864 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Saleh, J. E. Angermann, W. R. Sones, N. Leblanc, and I. A. Greenwood Stimulation of Ca2+-Gated Cl- Currents by the Calcium-Dependent K+ Channel Modulators NS1619 [1,3-Dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one] and Isopimaric Acid J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 1075 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. I. Jabr, A. J. Wilson, M. H. Riddervold, A. H. Jenkins, B. A. Perrino, and L. H. Clapp Nuclear translocation of calcineurin Abeta but not calcineurin A{alpha} by platelet-derived growth factor in rat aortic smooth muscle Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2213 - C2225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Angermann, A. R. Sanguinetti, J. L. Kenyon, N. Leblanc, and I. A. Greenwood Mechanism of the Inhibition of Ca2+-Activated Cl- Currents by Phosphorylation in Pulmonary Arterial Smooth Muscle Cells J. Gen. Physiol., June 26, 2006; 128(1): 73 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Saleh and I. A. Greenwood Activation of chloride currents in murine portal vein smooth muscle cells by membrane depolarization involves intracellular calcium release Am J Physiol Cell Physiol, January 1, 2005; 288(1): C122 - C131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A. Greenwood, J. Ledoux, A. Sanguinetti, B. A. Perrino, and N. Leblanc Calcineurin A{alpha} but Not A{beta} Augments ICl(Ca) in Rabbit Pulmonary Artery Smooth Muscle Cells J. Biol. Chem., September 10, 2004; 279(37): 38830 - 38837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Robinson, P. Huang, M. A. Kaetzel, F. S. Lamb, and D. J. Nelson Identification of an N-terminal amino acid of the CLC-3 chloride channel critical in phosphorylation-dependent activation of a CaMKII-activated chloride current J. Physiol., April 15, 2004; 556(2): 353 - 368. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
