Endothelium-dependent vasodilation in myogenically active mouse skeletal muscle arterioles: Role of EDH and K+ channels

Simon Potocnik, Iain McSherry, Hong Ding, Timothy Murphy, Neela Kotecha, Kim Dora, Kathryn Yuill, Christopher Triggle, Michael Hill

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

As smooth muscle cell (SMC) membrane potential (Em) is critical for vascular responsiveness, and arteriolar SMCs are depolarized at physiological intraluminal pressures, we hypothesized that myogenic tone impacts on dilation mediated by endothelium-derived hyperpolarization (EDH). Studies were performed on cannulated mouse cremaster arterioles [diameter, 33 ± 2 μm (n = 23) at 60 mmHg; SMC Em -34.6 ± 1.2 mV (n = 7)]. Myogenic activity was assessed as tone developed in response to intraluminal pressure. Functional observations were related to mRNA, protein expression, and anatomy. Acetylcholine concentration-response curves showed a modest shift following indomethacin (10 μM) and L-NAME (100 μM), although maximal vasodilation was achieved. Residual dilation was removed by apamin (1 μM) in combination with TRAM-34 (1 μM) or charybotoxin (0.1 μM), indicating the requirement of small (S) and intermediate (I) calcium-activated potassium channels (KCa). Charybdotoxin, but not TRAM-34, caused vasoconstriction, presumably through the inhibition of SMC BKCa. Expression of SK3 and IK1 was confirmed by immunohistochemistry and polymerase chain reaction, while myoendothelial junctions were common, suggesting a high degree of cell coupling. Also consistent with a role for endothelial KCa channels, acetylcholine increased endothelium [Ca2+]i. Apamin and TRAM-34 similarly blocked EDH-mediated dilation at intraluminal pressures of 30 and 90 mmHg, suggesting that in mouse arterioles, SKCa- and IKCa- mediated mechanisms predominate and operate independently of physiological levels of myogenic activation.

Original languageEnglish
Pages (from-to)377-390
Number of pages14
JournalMicrocirculation
Volume16
Issue number5
DOIs
Publication statusPublished - 2009
Externally publishedYes

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Keywords

  • Arteriole
  • Ca-activated K channel
  • EDH
  • Endothelium
  • Microcirculation
  • Myogenic

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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