title: Calcium-activated potassium channels contribute to human skeletal muscle microvascular endothelial dysfunction related to cardiopulmonary bypass.
abstract: 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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Eric W
authors.initials: EW
authors.lastname: Sellke
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Richard T
authors.initials: RT
authors.lastname: Clements
authors.forename: Neel R
authors.initials: NR
authors.lastname: Sodha
authors.forename: Kamal R
authors.initials: KR
authors.lastname: Khabbaz
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Senthilnathan
authors.forename: Seth L
authors.initials: SL
authors.lastname: Alper
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000368:Aged; D001030:Apamin / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D010091:Oximes / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D014662:Vasoconstrictor Agents; D014664:Vasodilation
chemical_list: C493327:6,7-dichloro-1H-indole-2,3-dione 3-oxime; D001562:Benzimidazoles; D007211:Indoles; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010091:Oximes; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011720:Pyrazoles; D051640:Small-Conductance Calcium-Activated Potassium Channels; C411671:TRAM 34; D014662:Vasoconstrictor Agents; C086491:NS 1619; D001030:Apamin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C064719:iberiotoxin