TRPC3 mediates pyrimidine receptor-induced depolarization of cerebral arteries.
We tested the hypothesis that TRPC3, a member of the canonical transient receptor potential (TRP) family of channels, mediates agonist-induced depolarization of arterial smooth muscle cells (SMCs). In support of this hypothesis, we observed that suppression of arterial SMC TRPC3 expression with antisense oligodeoxynucleotides significantly decreased the depolarization and constriction of intact cerebral arteries in response to UTP. In contrast, depolarization and contraction of SMCs induced by increased intravascular pressure, i.e., myogenic responses, were not altered by TRPC3 suppression. Interestingly, UTP-evoked responses were not affected by suppression of a related TRP channel, TRPC6, which was previously found to be involved in myogenic depolarization and vasoconstriction. In patch-clamp experiments, UTP activated a whole cell current that was greatly reduced or absent in TRPC3 antisense-treated SMCs. These results indicate that TRPC3 mediates UTP-induced depolarization of arterial SMCs and that TRPC3 and TRPC6 may be differentially regulated by receptor activation and mechanical stimulation, respectively.
Reading
S A
SA
Department of Pharmacology, University of Vermont, Burlington, Vermont 05405, USA. sreading@uvm.edu
Earley
S
S
Waldron
B J
BJ
Welsh
D G
DG
Brayden
J E
JE
D000818:Animals; D002536:Cerebral Arteries / Q000166:cytology / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D015870:Gene Expression; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D050052:TRPC Cation Channels; D014544:Uridine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D007473:Ion Channels; D016376:Oligonucleotides, Antisense; D011956:Receptors, Cell Surface; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C074644:uridine triphosphate receptors; D014544:Uridine Triphosphate