| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California School of Medicine, San Diego, California 92103-8382
Nitric oxide (NO) is an endogenous endothelium-derived relaxing factor that regulates vascular smooth muscle cell proliferation and apoptosis. This study investigated underlying mechanisms involved in NO-induced apoptosis in human and rat pulmonary artery smooth muscle cells (PASMC). Exposure of PASMC to NO, which was derived from the NO donor S-nitroso-N-acetyl-penicillamine, increased the percentage of cells undergoing apoptosis. Increasing extracellular K+ concentration to 40 mM or blocking K+ channels with 1 mM tetraethylammonia (TEA), 100 nM iberiotoxin (IBTX), and 5 mM 4-aminopyridine (4-AP) significantly inhibited the NO-induced apoptosis. In single PASMC, NO reversibly increased K+ currents through the large-conductance Ca2+-activated K+ (KCa) channels, whereas TEA and IBTX markedly decreased the KCa currents. In the presence of TEA, NO also increased K+ currents through voltage-gated K+ (Kv) channels, whereas 4-AP significantly decreased the Kv currents. Opening of KCa channels with 0.3 mM dehydroepiandrosterone increased KCa currents, induced apoptosis, and further enhanced the NO-mediated apoptosis. Furthermore, NO depolarized the mitochondrial membrane potential. These observations indicate that NO induces PASMC apoptosis by activating KCa and Kv channels in the plasma membrane. The resulting increase in K+ efflux leads to cytosolic K+ loss and eventual apoptosis volume decrease and apoptosis. NO-induced apoptosis may also be related to mitochondrial membrane depolarization in PASMC.
mitochondrial membrane potential; calcium; artery; potassium current
This article has been cited by other articles:
|
|
 |
|
  E. A. Ko, E. D. Burg, O. Platoshyn, J. Msefya, A. L. Firth, and J. X.-J. Yuan Functional characterization of voltage-gated K+ channels in mouse pulmonary artery smooth muscle cells Am J Physiol Cell Physiol, September 1, 2007; 293(3): C928 - C937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Remillard, D. D. Tigno, O. Platoshyn, E. D. Burg, E. E. Brevnova, D. Conger, A. Nicholson, B. K. Rana, R. N. Channick, L. J. Rubin, et al. Function of Kv1.5 channels and genetic variations of KCNA5 in patients with idiopathic pulmonary arterial hypertension Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1837 - C1853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Fantozzi, O. Platoshyn, A. H. Wong, S. Zhang, C. V. Remillard, M. R. Furtado, O. V. Petrauskene, and J. X.-J. Yuan Bone morphogenetic protein-2 upregulates expression and function of voltage-gated K+ channels in human pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L993 - L1004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Brevnova, O. Platoshyn, S. Zhang, and J. X.-J. Yuan Overexpression of human KCNA5 increases IK(V) and enhances apoptosis Am J Physiol Cell Physiol, September 1, 2004; 287(3): C715 - C722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Newman, B. L. Fanburg, S. L. Archer, D. B. Badesch, R. J. Barst, J. G.N. Garcia, P. N. Kao, J. A. Knowles, J. E. Loyd, M. D. McGoon, et al. Pulmonary Arterial Hypertension: Future Directions: Report of a National Heart, Lung and Blood Institute/Office of Rare Diseases Workshop Circulation, June 22, 2004; 109(24): 2947 - 2952. [Full Text] [PDF]
|
|
|
|
|
|
C. V. Remillard and J. X.-J. Yuan Activation of K+ channels: an essential pathway in programmed cell death Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L49 - L67. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
