| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia, USA
* To whom correspondence should be addressed. E-mail: sbarman{at}mail.mcg.edu.
Normally, signaling mechanisms which activate large-conductance, calcium- and voltage-activated potassium (BKCa) channels in pulmonary vascular smooth muscle cause pulmonary vasodilatation. BKCa channel modulation is important in the regulation of pulmonary arterial pressure and inhibition (decrease in the opening probability) of the BKCa channel has been implicated in the development of pulmonary vasoconstriction. Protein kinase C (PKC) causes pulmonary vasoconstriction, but little is known about the
effect of PKC on BKCa channel activity in pulmonary vascular smooth muscle. Accordingly, studies were done to determine the effect of PKC on BKCa channel activity using patch-clamp studies in pulmonary arterial smooth muscle (PASMC) cells of the Sprague-Dawley rat (SDR). The PKC activators phorbol myristate acetate (PMA) and thymeleatoxin, opened BKCa channels in single SDR PASMC. The activator response to both PMA and thymeleatoxin on BKCa channel activity was blocked by Go 6983, which selectively blocks the 
, 
, 
, 
and 
PKC isozymes and by rottlerin, which selectively inhibits PKC. In addition, the specific cGMP-dependent protein kinase (PKG) antagonist KT 5823 blocked the responses to PMA and thymelatoxin, while the specific cAMPdependent protein kinase (PKA) blocker KT 5720 had no effect. In isolated pulmonary arterial vessels, both PMA and forskolin caused vasodilatation, which was inhibited by either KT 5823, Go 6983 or the BKCa channel blocker TEA. The results of this study indicate that activation of specific PKC isozymes increases BKCa channel activity in SDR PASMC via PKG, which suggests a unique signaling mechanism for vasodilatation.
This article has been cited by other articles:
|
|
 |
|
  A. Goel, D. Thor, L. Anderson, and R. Rahimian Sexual dimorphism in rabbit aortic endothelial function under acute hyperglycemic conditions and gender-specific responses to acute 17{beta}-estradiol Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2411 - H2420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Chicoine, M. L. Paffett, M. R. Girton, M. J. Metropoulus, M. S. Joshi, J. A. Bauer, L. D. Nelin, T. C. Resta, and B. R. Walker Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1261 - L1270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Essin, B. Salanova, R. Kettritz, M. Sausbier, F. C. Luft, D. Kraus, E. Bohn, I. B. Autenrieth, A. Peschel, P. Ruth, et al. Large-conductance calcium-activated potassium channel activity is absent in human and mouse neutrophils and is not required for innate immunity Am J Physiol Cell Physiol, July 1, 2007; 293(1): C45 - C54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ledoux, M. E. Werner, J. E. Brayden, and M. T. Nelson Calcium-Activated Potassium Channels and the Regulation of Vascular Tone Physiology, February 1, 2006; 21(1): 69 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zhou, L. Liu, and D. Hu Involvement of BKCa {alpha} subunit tyrosine phosphorylation in vascular hyporesponsiveness of superior mesenteric artery following hemorrhagic shock in rats Cardiovasc Res, November 1, 2005; 68(2): 327 - 335. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
