Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 591, Issue 20, Pages 5031-5046Publisher
WILEY
DOI: 10.1113/jphysiol.2013.258319
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Funding
- NIH/NHLBI [HL67061, HL94378, HL110347]
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Intravascular pressure-induced vasoconstriction is a smooth muscle cell-specific mechanism that controls systemic blood pressure and organ regional blood flow. Smooth muscle cell polycystin-1 and -2 (TRPP1 and -2) proteins modulate the myogenic response in mesenteric arteries, but involvement in other vascular beds is unclear. Here, we examined TRPP2 expression, cellular distribution, cation currents (I-Cat), and physiological functions in smooth muscle cells of rat and human cerebral arteries. We demonstrate that TRPP2 is the major TRPP isoform expressed in cerebral artery smooth muscle cells, with message levels higher than those of TRPP1. Arterial biotinylation and immunofluorescence indicated that TRPP2 is located primarily (approximate to 88%) in the smooth muscle cell plasma membrane. RNA interference reduced TRPP2 expression by approximate to 55% compared to control, but did not alter levels of TRPP1, TRPC1, TRPC3, TRPC6, TRPM4, ANO1/TMEM16A, or voltage-dependent Ca2+ (Ca(V)1.2) channels, other ion channel proteins that modulate myogenic tone. Cell swelling induced by hyposmotic (250 osmol (l solution)(-1)) bath solution stimulated Gd3+-sensitive I-Cat in smooth muscle cells that were reduced by selective TRPP2 knockdown. TRPP2 knockdown did not alter myogenic tone at 20 mmHg but reduced tone between approximate to 28 and 39% over an intravascular pressure range between 40 and 100 mmHg. In contrast, TRPP2 knockdown did not alter depolarization-induced (60 mmol l K+) vasoconstriction. In summary, we show that TRPP2 is expressed in smooth muscle cells of resistance-size cerebral arteries, resides primarily in the plasma membrane, and contributes to the myogenic response. Data also suggest that TRPP2 differentially regulates the myogenic response in cerebral and mesenteric arteries.
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