RT info:eu-repo/semantics/article
T1 Differences in TRPC3 and TRPC6 channels assembly in mesenteric vascular smooth muscle cells in essential hypertension
A1 Álvarez Miguel, Inés
A1 Cidad Velasco, María del Pilar
A1 Pérez García, María Teresa
A1 López López, José Ramón
K1 Arterial smooth muscle
K1 Músculo liso vascular
K1 Hypertension
K1 Hipertensión
AB Increased vascular tone in essential hypertension involves a sustained rise in total peripheral resistance. A model has been proposed in which the combination of membrane depolarization and higher L‐type Ca2+ channel activity generates augmented Ca2+ influx into vascular smooth muscle cells (VSMCs), contraction and vasoconstriction. The search for culprit ion channels responsible for membrane depolarization has provided several candidates, including members of the canonical transient receptor potential (TRPC) family. TRPC3 and TRPC6 are diacylglycerol‐activated, non‐selective cationic channels contributing to stretch‐ or agonist‐induced depolarization. Conflicting information exists regarding changes in TRPC3/TRPC6 functional expression in hypertension. However, although TRPC3‐TRPC6 channels can heteromultimerize, the possibility that differences in their association pattern may change their functional contribution to vascular tone is largely unexplored. We probe this hypothesis using a model of essential hypertension (BPH mice; blood pressure high) and its normotensive control (BPN mice; blood pressure normal). First, non‐selective cationic currents through homo‐ and heterotetramers recorded from transfected Chinese hamster ovary cells indicated that TRPC currents were sensitive to the selective antagonist Pyr10 only when TRPC6 was present, whereas intracellular anti‐TRPC3 antibody selectively blocked TRPC3‐mediated currents. In mesenteric VSMCs, basal and agonist‐induced currents were more sensitive to Pyr3 and Pyr10 in BPN cells. Consistently, myography studies showed a larger Pyr3/10‐induced vasodilatation in BPN mesenteric arteries. mRNA and protein expression data supported changes in TRPC3 and TRPC6 proportions and assembly, with a higher TRPC3 channel contribution in BPH VSMCs that could favour cell depolarization. These differences in functional and pharmacological properties of TRPC3 and TRPC6 channels, depending on their assembly, could represent novel therapeutical opportunities.
PB The Physiological Society
SN 1469-7793
YR 2016
FD 2016
LK http://uvadoc.uva.es/handle/10324/44482
UL http://uvadoc.uva.es/handle/10324/44482
LA eng
NO The Journal of Physiology, 2017, vol. 595, n. 5. p. 1497-1513
NO Producción Científica
DS UVaDOC
RD 24-nov-2024