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
Received:15 August 2017,
Revised:2017-11-15,
Published:15 February 2018
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Yanjun GUO, Jingjing LIU, Hanxing WAN, et al. Regulatory roles of Kv1.1 and Kv1.3 channel subtypes in mouse mesenteric arterioles
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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