Transient receptor potential channels regulate myogenic tone of resistance arteries.
Elevation of intravascular pressure causes depolarization and constriction (myogenic tone) of small arteries and arterioles, and this response is a key element in blood flow regulation. However, the nature of pressure-induced depolarization has remained elusive. In the present study, we provide evidence that a transient receptor potential channel (TRPC6) homologue has a major role in this depolarizing response to pressure. Antisense oligodeoxynucleotides to TRPC6 decreased TRPC6 protein expression and greatly attenuated arterial smooth muscle depolarization and constriction caused by elevated pressure in intact cerebral arteries. Suppressing the expression of this channel protein also reduced the current density of a major cation current in resistance artery smooth muscle cells. We propose that TRPC6 channels play an essential role in regulation of myogenic tone.
Welsh
Donald G
DG
Department of Pharmacology, University of Vermont, College of Medicine, Burlington, Vt 05405, USA.
Morielli
Anthony D
AD
Nelson
Mark T
MT
Brayden
Joseph E
JE
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D015153:Blotting, Western; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002536:Cerebral Arteries / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D015220:Calcium Channels; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat