Copyright © 2007, European Society of Cardiology
Mechanosensitive nonselective cation channel facilitation by endothelin-1 is regulated by protein kinase C in arterial myocytes
aDepartment of Physiology, Heart Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
bDepartment of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea
*Corresponding author. Tel.: +82 2 740 8230; fax: +82 2 763 9667. sjoonkim{at}snu.ac.kr
Objective The mechanosensitive nonselective cation channel (NSCMS) and endothelin-1 (ET-1) play critical roles in the regulation of vascular tone. This study was undertaken to investigate the effect of ET-1 on NSCMS and on the myogenic response of arteries.
Methods Cell-attached patch-clamp techniques were applied to rabbit pulmonary and cerebral arterial smooth muscle cells using a 140 mM CsCl pipette and bath solutions (Ca2+-free, 1 mM EGTA). Myogenic responses were determined by video analysis of pressurized arteries.
Results The application of negative pressures through the pipette activated NSCMS, and this was augmented by bath application of ET-1 (1 pM–30 nM). ET-1 lowered the lowest pressure required for NSCMS activation. NSCMS facilitation by ET-1 was prevented by BQ-123 (1 µM, an ETA antagonist) but not by BQ-788 (1 µM, an ETB antagonist). Phorbol 12-myristate 13-acetate (PMA, 100 nM), a protein kinase C activator, also increased the activity of NSCMS. ET-1- or PMA-induced facilitation of NSCMS was abolished by GF109203X (10 µM), a protein kinase C inhibitor. Video analysis of pressurized cerebral artery showed inhibition of the myogenic response by the NSCMS channel blockers GsMTx-4 (5 µM) and DIDS (3–100 µM). Treatment with ET-1 (10 pM) augmented the myogenic response and this was inhibited by DIDS (30 µM).
Conclusion Stimulation of ET-1 receptor (ETA) facilitates NSCMS via a protein kinase C-dependent signaling pathway in rabbit arterial myocytes. Our findings suggest that NSCMS play a role in the myogenic response and its augmentation by ET-1.
KEYWORDS Pulmonary artery; Smooth muscle; Mechanosensitive nonselective cation channel; Endothelin; protein kinase C; Myogenic response
[1] These authors contributed equally to this study.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Inoue, L. J. Jensen, Z. Jian, J. Shi, L. Hai, A. I. Lurie, F. H. Henriksen, M. Salomonsson, H. Morita, Y. Kawarabayashi, et al. Synergistic Activation of Vascular TRPC6 Channel by Receptor and Mechanical Stimulation via Phospholipase C/Diacylglycerol and Phospholipase A2/{omega}-Hydroxylase/20-HETE Pathways Circ. Res., June 19, 2009; 104(12): 1399 - 1409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Whitman, S. Pisarcik, T. Luke, M. Fallon, J. Wang, J. T. Sylvester, G. L. Semenza, and L. A. Shimoda Endothelin-1 mediates hypoxia-induced inhibition of voltage-gated K+ channel expression in pulmonary arterial myocytes Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L309 - L318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Coleman and H. C. Parkington Endothelin enhances activity of mechanosensitive channels: A mechanism for ET augmentation of the myogenic response Cardiovasc Res, November 1, 2007; 76(2): 197 - 198. [Full Text] [PDF]
|
|