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


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 (Ca(2+)-free, 1 mM EGTA). Myogenic responses were determined by video analysis of pressurized arteries.


RESULTS
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).


CONCLUSIONS
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.
Lee
Hyang Ae
HA
Department of Physiology, Heart Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Baek
Eun Bok
EB
Park
Kyung Sun
KS
Jung
Hoi Jong
HJ
Kim
Jae Il
JI
Kim
Sung Joon
SJ
Earm
Yung E
YE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D013111:Spider Venoms / Q000494:pharmacology; D013314:Stress, Mechanical; D050052:TRPC Cation Channels / Q000187:drug effects / Q000502:physiology; D000074287:TRPC6 Cation Channel; D050053:TRPM Cation Channels / Q000187:drug effects / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000502:physiology
D019332:Endothelin-1; D036341:Intercellular Signaling Peptides and Proteins; C411249:MTx4 protein, Grammostola spatulata; D010455:Peptides; D013111:Spider Venoms; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D050051:Transient Receptor Potential Channels; D011493:Protein Kinase C; D002118:Calcium