Sensing pressure in the cardiovascular system: Gq-coupled mechanoreceptors and TRP channels.
Despite the central physiological importance of cardiovascular mechanotransduction, the molecular identities of the sensors and the signaling pathways have long remained elusive. Indeed, how pressure is transduced into cellular excitation has only recently started to emerge. In both arterial and cardiac myocytes, the diacylglycerol-sensitive canonical transient receptor potential (TRPC) subunits are proposed to underlie the stretch-activated depolarizing cation channels. An indirect mechanism of activation through a ligand-independent conformational switch of Gq-coupled receptors by mechanical stress is invoked. Such a mechanism involving the angiotensin type 1 receptor and TRPC6 is proposed to trigger the arterial myogenic response to intraluminal pressure. TRPC6 is also involved in load-induced cardiac hypertrophy. In this review, we will focus on the molecular basis of pressure sensing in the cardiovascular system and associated disease states.
IPMC-CNRS, 660 route des Lucioles, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
Reza
R
Sharif-Naeini
Joost H A
JH
Folgering
Delphine
D
Bichet
Fabrice
F
Duprat
Patrick
P
Delmas
Amanda
A
Patel
Eric
E
Honoré
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology; D002319:Cardiovascular System / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D008465:Mechanoreceptors / Q000737:chemistry / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008954:Models, Biological; D050052:TRPC Cation Channels / Q000737:chemistry / Q000378:metabolism*
C011439:1,2-diacylglycerol; D004075:Diglycerides; D050052:TRPC Cation Channels