Smooth muscle cell transient receptor potential polycystin-2 (TRPP2) channels contribute to the myogenic response in cerebral arteries

Damodaran Narayanan, Simon Bulley, Marie Dennis Leo, Sarah K. Burris, Kyle S. Gabrick, Frederick Boop, Jonathan Jaggar

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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 (ICat), 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 (~88%) in the smooth muscle cell plasma membrane. RNA interference reduced TRPP2 expression by ~55% compared to control, but did not alter levels of TRPP1, TRPC1, TRPC3, TRPC6, TRPM4, ANO1/TMEM16A, or voltage-dependent Ca2+ (CaV1.2) channels, other ion channel proteins that modulate myogenic tone. Cell swelling induced by hyposmotic (250 osmol (l solution)-1) bath solution stimulated Gd3+-sensitive ICat 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 ~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.

Original languageEnglish (US)
Pages (from-to)5031-5046
Number of pages16
JournalJournal of Physiology
Volume591
Issue number20
DOIs
StatePublished - Oct 1 2013

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Cerebral Arteries
Smooth Muscle Myocytes
Mesenteric Arteries
Cell Membrane
Vasoconstriction
polycystic kidney disease 2 protein
Biotinylation
Pressure
Regional Blood Flow
RNA Interference
Baths
Ion Channels
Cell Size
Fluorescent Antibody Technique
Blood Vessels
Cations
Protein Isoforms
Proteins
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Smooth muscle cell transient receptor potential polycystin-2 (TRPP2) channels contribute to the myogenic response in cerebral arteries. / Narayanan, Damodaran; Bulley, Simon; Leo, Marie Dennis; Burris, Sarah K.; Gabrick, Kyle S.; Boop, Frederick; Jaggar, Jonathan.

In: Journal of Physiology, Vol. 591, No. 20, 01.10.2013, p. 5031-5046.

Research output: Contribution to journalArticle

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abstract = "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 (ICat), 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 (~88{\%}) in the smooth muscle cell plasma membrane. RNA interference reduced TRPP2 expression by ~55{\%} compared to control, but did not alter levels of TRPP1, TRPC1, TRPC3, TRPC6, TRPM4, ANO1/TMEM16A, or voltage-dependent Ca2+ (CaV1.2) channels, other ion channel proteins that modulate myogenic tone. Cell swelling induced by hyposmotic (250 osmol (l solution)-1) bath solution stimulated Gd3+-sensitive ICat 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 ~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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