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Constitutively active TRPC3 channels regulate membrane potential and adrenergic reactivity of mesenteric artery smooth muscle
Author(s) -
Reading Stacey Allan,
Drapp Rebecca Lea,
Brayden Joseph Elliot
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1242-d
Subject(s) - mesenteric arteries , membrane potential , phenylephrine , medicine , endocrinology , depolarization , trpc3 , vascular smooth muscle , chemistry , vasoconstriction , electrophysiology , artery , biology , transient receptor potential channel , receptor , smooth muscle , blood pressure , biochemistry , trpc
The canonical transient receptor potential channel TRPC3 is present in mesenteric artery smooth muscle cells (aSMCs) and we hypothesized that these channels are tonically active and regulate the aSMC resting membrane potential. Arteries (<300μm) from male Sprague‐Dawley rats (350g) were used immediately or placed into organ culture for 3 days. Western blots showed that organ culture decreased TRPC3 expression by nearly 60%. At 60mmHg intra‐arterial pressure, the aSMC resting membrane potential was significantly more polarized in cultured (−57±3 mV) than in fresh (−48±1 mV) arteries superfused with a physiologic saline containing 5mM KCl. Measurement of arterial diameter indicated a rightward shift in the dose response to phenylephrine (PHE) in cultured (EC 50 4.1x10 −6 M) vs. fresh (EC 50 6.4x10 −7 M) arteries. The differences between fresh and cultured arteries for resting membrane potential and PHE sensitivity were eliminated by superfusing the arteries with a physiologic saline containing 20mM KCl to depolarize the aSMCs; the resting membrane potentials were −40±3 and −39±1mV and the PHE EC 50 was 3.1x10 −7 M and 3.8x10 −7 M in cultured and fresh arteries respectively. In summary, tonic activity of TRPC3 channels depolarizes the mesenteric aSMCs, regulating sensitivity to the α 1 ‐adrenergic agonist PHE. Thus, constitutively active TRPC3 channels influence adrenergic vasoconstriction and contribute to mesenteric vascular resistance.