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400037 重庆,陆军军医大学(第三军医大学)第二附属医院消化内科
[ 董辉,E-mail:h2dong@ucsd.eduDONG Hui, E-mail:h2dong@ucsd.edu
收稿:2017-08-15,
修回:2017-11-15,
纸质出版:2018-02-15
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郭艳军, 刘菁菁, 万晗星, 等. Kv1.1及Kv1.3通道亚型对小鼠肠系膜微细动脉的调节作用[J]. 第三军医大学学报, 2018,40(3):190-197.
Yanjun GUO, Jingjing LIU, Hanxing WAN, et al. Regulatory roles of Kv1.1 and Kv1.3 channel subtypes in mouse mesenteric arterioles
郭艳军, 刘菁菁, 万晗星, 等. Kv1.1及Kv1.3通道亚型对小鼠肠系膜微细动脉的调节作用[J]. 第三军医大学学报, 2018,40(3):190-197. DOI: 10.16016/j.1000-5404.201708202.
Yanjun GUO, Jingjing LIU, Hanxing WAN, et al. Regulatory roles of Kv1.1 and Kv1.3 channel subtypes in mouse mesenteric arterioles
目的
2
研究Kv1.1及Kv1.3通道亚型对小鼠肠系膜微细血管的调节作用。
方法
2
以健康6~8周C57BL/6雄性小鼠肠系膜微细动脉作为研究对象,应用丹麦DMT520A离体微血管张力测定系统记录血管张力变化。应用广谱电压依赖性钾通道(Kv)阻断剂4-AP,Kv1.3通道选择性阻断剂PAP-1,Kv1.1通道选择性阻断剂TEA分别作用于静息状态,KCl及NE预收缩动脉,记录血管张力变化情况。应用Kv通道阻断剂4-AP,Kv1.3通道选择性阻断剂PAP-1作用于血管,观察Kv及Kv1.3通道在0 mmol/L Ca
2+
及2 mmol/L Ca
2+
K-H液中对NE收缩曲线的作用。
结果
2
Kv通道阻断剂4-AP可引起静息状态的血管收缩,并进一步收缩KCl预收缩的血管,但浓度依赖性舒张NE预收缩的动脉,并且与对照组相比,4-AP能明显抑制NE在0 mmol/L Ca
2+
液中所致的血管收缩[(3.45±0.24)mN
vs
(0.11±0.02)mN
P
<
0.01
]
。Kv1.3通道选择性阻断剂PAP-1未能收缩静息状态的血管,但可使KCl预收缩的血管发生轻微舒张反应,却明显舒张NE预收缩的动脉,而且PAP-1既可抑制NE在0 mmol/L Ca
2+
K-H液中所致的血管收缩[对照组
vs
PAP-1组:(4.28±0.53)mN
vs
(2.75±0.49)mN
P
<
0.05
]
,又可抑制在2 mmol/L Ca
2+
液中的收缩张力[对照组
vs
PAP-1组:(7.08±0.58)mN
vs
(5.90±0.80)mN
P
<
0.05
]
。Kv1.1通道选择性阻断剂TEA可引起静息状态的血管收缩,但在0 mmol/L Ca
2+
液中该作用消失,同时对KCl或NE预收缩的动脉均无明显作用。
结论
2
Kv通道可调节小鼠肠系膜动脉的舒缩反应。其中Kv1.1通道主要发挥血管收缩调节作用,可能与促进血管平滑肌细胞外钙内流有关,而Kv1.3通道主要发挥血管舒张调节作用,可能同时抑制平滑肌细胞内钙释放和细胞外钙内流。
Objective
2
To determine the regulatory roles of Kv1.1 and Kv1.3 channel subtypes on mouse mesenteric arterioles and to elucidate the underlying mechanisms.
Methods
2
Mesenteric arterioles were isolated from 6 to 8 weeks old healthy male C57BL/6 mice. Tension changes of the isolated mesenteric arterioles were recorded with DMT520
A myograph system. Then
4-aminopyridine (4-AP)[broad-spectrum blcoker of voltage-dependent potassium channel(Kv)
]
PAP-1 (selective blocker of Kv1.3 channel)
and tetraethylam-monium (TEA
selective blocker of Kv1.1 channel) were used respectively to act on resting
norepinephrine (NE)-precontracted and KCl-precontracted vessels
and the changes of vascular tone were recorded. Then 4-AP and PAP-1 were used to treat mesenteric arterioles to explore the effect of Kv channel and Kv1.3 channel on NE contraction curve in 0 mmol/L Ca
2+
and 2 mmol/L Ca
2+
K-H solutions.
Results
2
4-AP induced the contraction in both resting and KCl-precontracted vessels
but it also induced vasorelaxation of NE-precontracted mesenteric arterioles. Compared with control group
4-AP treatment significantly inhibited NE-induced vasoconstriction in 0 mmol/L Ca
2+
K-H solution (3.45±0.24
vs
0.11±0.02 mN
P
<
0.01). PAP-1 did not alter resting mesenteric arterioles
but caused a slight relaxation and marked diastole of NE-precontracted and KCl-precontracted vessels
respectively. Besides
PAP-1 not only inhibited the vasoconstriction mediated by NE in 0 mmol/L Ca
2+
K-H solution (control
vs
PAP-1 group: 4.28±0.53
vs
2.75±0.49 mN
P
<
0.05)
but also in 2 mmol/L Ca
2+
solution (control
vs
PAP-1 group: 7.08±0.58
vs
5.90±0.80 mN
P
<
0.05). TEA also induced the contraction of resting vessels
but this effect disappeared in 0 mmol/L Ca
2+
solution. What’s more
TEA did not alert either KCl-or NE-precontracted vessels.
Conclusion
2
Kv channels can regulate the contractility of mouse mesenteric arterioles. Kv1.1 channel may mainly mediate vasoconstriction
via
promoting extracellular calcium influx. However
Kv1.3 channel may mainly mediate vasodilatation through inhibitin
g both intracellular calcium release and extracellular calcium influx.
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