Large Conductance Calcium-Activated Potassium Channels Contribute to the Reduced Myogenic Tone of Peripheral Microvasculature After Cardiopulmonary Bypass

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• 作者：Jun Feng ; Yuhong Liu ; Kamal R. Khabbaz ; Neel R. Sodha ; Robert M. Osipov ; Robert Hagberg ; Seth L. Alper ; Frank W. Sellke
• 关键词：calcium-activated potassium channels ; cardiopulmonary bypass ; myogenic tone ; vasomotor dysfunction ; microcirculation ; human ; skeletal muscle
• 刊名：Journal of Surgical Research
• 出版年：2009
• 出版时间：November 2009
• 年：2009
• 卷：157
• 期：1
• 页码：123-128
• 全文大小：658 K

文摘

Background

We investigated the role of calcium-activated potassium (K_Ca) channel activation in myogenic tone in human peripheral microvasculature after heart surgery.

Methods

Human skeletal muscle arterioles (90–180 μm diameter) were dissected from tissue harvested pre- and post-cardiopulmonary bypass (CPB) during cardiac surgery. Myogenic reactivity in response to stepwise increases in intraluminal pressure was studied between pressure steps. Microvessel tone was determined pre-CPB, post-CPB, and after blockade of K_Ca channels. Expression and localization of large conductance (BK) K_Ca channels in the coronary microvasculature was assessed by immunoblot and immunofluorescence photomicroscopy.

Results

Myogenic tone of skeletal muscle arterioles was significantly reduced post-CPB compared with pre-CPB. Decrease in myogenic tone after CPB was reflected by the increase in microvessel internal diameter. Myogenic tone of post-CPB microvessels was significantly increased after treatment with BK_Ca-blocker iberiotoxin, but unchanged in the combined presence of the blockers of intermediate (IK_Ca) and small conductance (SK_Ca) K_Ca channels, TRAM34/apamin. The increases in myogenic tone after iberiotoxin treatment were demonstrated as a decrease in microvessel internal diameter. No significant differences in BK_Ca protein levels were noted comparing pre- and post-CPB conditions judged by immunoblot and by immunofluorescence staining of skeletal muscle microvessels. Prominent staining for BK_Ca-α and BK_Ca-β₁ subunits localized to the microvascular smooth muscle.

Conclusion

CPB-associated decrease in peripheral myogenic reactivity is likely due to activation of BK_Ca, but not IK_Ca or SK_Ca. CPB may increase BK_Ca activity without increasing BK polypeptide level.