Calcium-activated potassium channels contribute to human skeletal muscle microvascular endothelial dysfunction related to cardiopulmonary bypass

Surgery. 2008 Aug;144(2):239-44. doi: 10.1016/j.surg.2008.03.032.


Background: We investigated the role of calcium-activated potassium (K(Ca)) channel activity in human skeletal muscle microvascular function in the setting of cardiopulmonary bypass (CPB).

Methods and results: Human skeletal muscle arterioles (80- to 180 microm in diameter) were dissected from tissue harvested before and after CPB. In vitro relaxation responses of precontracted arterioles in a pressurized no-flow state were examined in the presence of K(Ca) channel activators/blockers and several other vasodilators. Post-CPB responses to the activator of intermediate (IK(Ca)) and small conductance (SK(Ca)) K(Ca) channels, NS309, to the endothelium-dependent vasodilator adenosine 5'-diphosphate (ADP), and to substance P were reduced compared with pre-CPB responses (P < .05), respectively, whereas responses to the activator of large conductance (BK(Ca)) K(Ca) channels, NS1619, and to the endothelium-independent vasodilator, sodium nitroprusside (SNP) were unchanged. Endothelial denudation decreased NS309-induced relaxation and abolished that induced by ADP or substance P (P < .05), but had no effect on relaxation induced by either NS1619 or SNP. Polypeptide levels of BK(Ca), IK(Ca), and SK3(Ca) were not altered post-CPB.

Conclusion: IK/SK-mediated relaxation is predominantly endothelium dependent, whereas BK-mediated relaxation seems to be largely independent of endothelial function in human skeletal muscle microvasculature. CPB-associated microvascular dysfunction likely arises in part from impaired function of endothelial SK and IK channels in the peripheral microvasculature.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Aged
  • Apamin / pharmacology
  • Benzimidazoles / pharmacology
  • Cardiopulmonary Bypass / adverse effects*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • In Vitro Techniques
  • Indoles / pharmacology
  • Intermediate-Conductance Calcium-Activated Potassium Channels / metabolism
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism
  • Male
  • Muscle, Skeletal / blood supply*
  • Oximes / pharmacology
  • Peptides / pharmacology
  • Potassium Channels
  • Potassium Channels, Calcium-Activated / metabolism*
  • Pyrazoles / pharmacology
  • Small-Conductance Calcium-Activated Potassium Channels / metabolism
  • Vasoconstrictor Agents
  • Vasodilation


  • 6,7-dichloro-1H-indole-2,3-dione 3-oxime
  • Benzimidazoles
  • Indoles
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Large-Conductance Calcium-Activated Potassium Channels
  • Oximes
  • Peptides
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Pyrazoles
  • Small-Conductance Calcium-Activated Potassium Channels
  • TRAM 34
  • Vasoconstrictor Agents
  • NS 1619
  • Apamin
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • iberiotoxin