Transient receptor potential (TRP) channels, vascular tone and autoregulation of cerebral blood flow.
Members of the transient receptor potential (TRP) channel superfamily are present in vascular smooth muscle cells and play important roles in the regulation of vascular contractility. The TRPC3 and TRPC6 channels are activated by stimulation of several excitatory receptors in vascular smooth muscle cells. Activation of these channels leads to myocyte depolarization, which stimulates Ca2+ entry via voltage-dependent Ca2+ channels (VDCC), leading to vasoconstriction. The TRPV4 channels in arterial myocytes are activated by epoxyeicosatrienoic acids, and activation of the channels enhances Ca2+ spark and transient Ca2+-sensitive K+ channel activity, thereby hyperpolarizing and relaxing vascular smooth muscle cells. The TRPC6 and TRPM4 channels are activated by mechanical stimulation of cerebral artery myocytes. Subsequent depolarization and activation of VDCC Ca2+ entry is directly linked to the development of myogenic tone in vitro and to autoregulation of cerebral blood flow in vivo. These findings imply a fundamental importance of TRP channels in the regulation of vascular smooth muscle tone and suggest that TRP channels could be important targets for drug therapy under conditions in which vascular contractility is disturbed (e.g. hypertension, stroke, vasospasm).
Brayden
Joseph E
JE
Department of Pharmacology, The University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405, USA. joe.brayden@uvm.edu
Earley
Scott
S
Nelson
Mark T
MT
Reading
Stacey
S
D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004537:Eicosanoic Acids / Q000494:pharmacology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000378:metabolism / Q000502:physiology*; D014652:Vascular Diseases / Q000209:etiology; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000378:metabolism / Q000502:physiology
D004537:Eicosanoic Acids; D050051:Transient Receptor Potential Channels