Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
Am J Physiol Heart Circ Physiol. 2011 Feb;300(2):H476-85. doi: 10.1152/ajpheart.00975.2010. Epub 2010 Dec 3.
Large-conductance Ca2+-activated K+ (BK) channels are composed of pore-forming α-subunits and accessory β1-subunits that modulate Ca2+ sensitivity. BK channels regulate arterial myogenic tone and renal Na+ clearance/K+ reabsorption. Previous studies using indirect or short-term blood pressure measurements found that BK channel β1-subunit knockout (BK β1-KO) mice were hypertensive. We evaluated 24-h mean arterial pressure (MAP) and heart rate in BK β1-KO mice using radiotelemetry. BK β1-KO mice did not have a higher 24-h average MAP when compared with wild-type (WT) mice, although MAP was ∼10 mmHg higher at night. The dose-dependent peak declines in MAP by nifedipine were only slightly larger in BK β1-KO mice. In BK β1-KO mice, giving 1% NaCl to mice to drink for 7 days caused a transient (5 days) elevation of MAP (∼5 mmHg); MAP returned to pre-saline levels by day 6. BK β1-KO mesenteric arteries in vitro demonstrated diminished contractile responses to paxilline, increased reactivity to Bay K 8644 and norepinephrine (NE), and maintained relaxation to isoproterenol. Paxilline and Bay K 8644 did not constrict WT or BK β1-KO mesenteric veins (MV). BK β1-subunits are not expressed in MV. The results indicate that BK β1-KO mice are not hypertensive on normal or high-salt intake. BK channel deficiency increases arterial reactivity to NE and L-type Ca2+ channel function in vitro, but the L-type Ca2+ channel modulation of MAP is not altered in BK β1-KO mice. BK and L-type Ca(2+) channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension.
大电导钙激活钾 (BK) 通道由孔形成的 α 亚基和调节钙敏感性的辅助 β1 亚基组成。BK 通道调节动脉肌源性张力和肾脏钠清除/钾重吸收。先前使用间接或短期血压测量的研究发现，BK 通道 β1 亚基敲除 (BK β1-KO) 小鼠患有高血压。我们使用无线电遥测评估了 BK β1-KO 小鼠的 24 小时平均动脉压 (MAP) 和心率。与野生型 (WT) 小鼠相比，BK β1-KO 小鼠的 24 小时平均 MAP 并没有更高，尽管夜间 MAP 高约 10mmHg。硝苯地平的剂量依赖性 MAP 峰值下降在 BK β1-KO 小鼠中仅略大。在 BK β1-KO 小鼠中，给予 1% NaCl 让小鼠饮用 7 天导致 MAP 短暂（5 天）升高（约 5mmHg）；到第 6 天 MAP 恢复到生理盐水水平。体外 BK β1-KO 肠系膜动脉对 paxilline 的收缩反应减弱，对 Bay K 8644 和去甲肾上腺素 (NE) 的反应性增加，对异丙肾上腺素的舒张反应保持不变。paxilline 和 Bay K 8644 不能收缩 WT 或 BK β1-KO 肠系膜静脉 (MV)。BK β1 亚基不在 MV 中表达。结果表明，在正常或高盐摄入时，BK β1-KO 小鼠没有高血压。BK 通道缺乏增加了动脉对 NE 和 L 型钙通道功能的反应性，但在 BK β1-KO 小鼠中，MAP 的 L 型钙通道调节没有改变。BK 和 L 型钙 (Ca 2+) 通道不调节小鼠静脉张力。似乎动脉中选择性丧失 BK 通道功能不足以导致持续高血压。
