Mechanosensitive nonselective cation channel facilitation by endothelin-1 is regulated by protein kinase C in arterial myocytes

• Published in: Cardiovascular research Vol. 76; no. 2; pp. 224 - 235
• Main Authors: HYANG AE LEE, EUN BOK BAEK, KYUNG SUN PARK, HOI JONG JUNG, JAE IL KIM, SUNG JOON KIM, EARM, Yung E
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-11-2007
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Cardiology. Vascular system; Endothelin-1 - pharmacology; Female; Humans; Male; Medical sciences; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - physiology; Peptides - pharmacology; Protein Kinase C - physiology; Pulmonary Artery - cytology; Pulmonary Artery - drug effects; Pulmonary Artery - physiology; Rabbits; Spider Venoms - pharmacology; Stress, Mechanical; Transient Receptor Potential Channels - drug effects; Transient Receptor Potential Channels - physiology; TRPC Cation Channels - drug effects; TRPC Cation Channels - physiology; TRPC6 Cation Channel; TRPM Cation Channels - drug effects; TRPM Cation Channels - physiology; Protein kinase C; Endothelin; Enzyme; Transferases; Smooth muscle; Ionic channel; Endothelin 1; Phlebology; Pulmonary artery; Myocyte; Response; Regulation(control); Myogenic response; Cations; Circulatory system; Cardiology; Mechanosensitive nonselective cation channel
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2007.06.021

The mechanosensitive nonselective cation channel (NSC(MS)) 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 NSC(MS) and on the myogenic response of arteries.
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 (Ca(2+)-free, 1 mM EGTA). Myogenic responses were determined by video analysis of pressurized arteries.
The application of negative pressures through the pipette activated NSC(MS), and this was augmented by bath application of ET-1 (1 pM-30 nM). ET-1 lowered the lowest pressure required for NSC(MS) activation. NSC(MS) facilitation by ET-1 was prevented by BQ-123 (1 microM, an ET(A) antagonist) but not by BQ-788 (1 microM, an ET(B) antagonist). Phorbol 12-myristate 13-acetate (PMA, 100 nM), a protein kinase C activator, also increased the activity of NSC(MS). ET-1- or PMA-induced facilitation of NSC(MS) was abolished by GF109203X (10 microM), a protein kinase C inhibitor. Video analysis of pressurized cerebral artery showed inhibition of the myogenic response by the NSC(MS) channel blockers GsMTx-4 (5 microM) and DIDS (3-100 microM). Treatment with ET-1 (10 pM) augmented the myogenic response and this was inhibited by DIDS (30 microM).
Stimulation of ET-1 receptor (ET(A)) facilitates NSC(MS) via a protein kinase C-dependent signaling pathway in rabbit arterial myocytes. Our findings suggest that NSC(MS) play a role in the myogenic response and its augmentation by ET-1.