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Disruption of Intermediate‐conductance Calcium‐activated Potassium Channels, KCa3.1, Unchanges NO‐dependent Relaxations in Mouse Aortas
Author(s) -
Ohta Masanori,
Miura Hiroto
Publication year - 2009
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.23.1_supplement.952.5
Subject(s) - chemistry , phenylephrine , sodium nitroprusside , hyperpolarization (physics) , extracellular , calcium , potassium channel , endocrinology , potassium , electrical impedance myography , calcium activated potassium channel , acetylcholine , medicine , vasodilation , biophysics , biochemistry , nitric oxide , stereochemistry , biology , nuclear magnetic resonance spectroscopy , organic chemistry , blood pressure
Endothelial NO release and vasorelaxation are preceded by KCa channel activation causing hyperpolarization, facilitated influx of extracellular calcium and NO synthesis in endothelial cells. The aim of this study was to investigate the precise role of KCa3.1 in vascular responses in mouse aortas. Methods Wire myography was performed using KCa3.1 +/+ (WT) and −/− (KO) mouse aortic rings precontracted with phenylephrine. Results Relaxation to acetylcholine (10 −10 to 10 −4 M) was identical between strains (%max relaxation: KO 78±5 p=ns vs WT 87±5% and EC 50 ; KO 4.4±1.4 p=ns vs WT 5.0±2.0 x 10 −8 M, n=5‐6) and was abolished by endothelial denudation. Nω‐nitro‐L‐arginine methyl ester significantly reduced the relaxation in both to a similar extent (WT 34±9 and KO 36±9%, p<0.05 vs control, respectively, n=7‐8), while indomethacin had no effect. No further reduction in relaxations was seen with the combination of inhibitors. Relaxation to sodium nitroprusside (10 −12 to 10 −4 M) was also unaltered in KO compared to WT (%max relaxation: KO 90±4 p=ns vs WT 83±8% and EC 50 ; KO 2.9±1.5 p=ns vs WT 21.3±13.6 x 10 −8 M, n=5‐6). Conclusion KCa3.1 alone plays no discernible role in mediating NO‐dependent vasorelaxation in mice, supporting a role for small‐conductance KCa channel either alone or in combination with KCa3.1. Supported by an NIH grant.