N-type calcium channels control sympathetic neurotransmission in human heart atrium
N-type calcium channels control sympathetic neurotransmission in human heart atrium
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DOI：
10.1161/01.cir.101.4.403
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发表时间：
2000-02-01
期刊：
影响因子：
37.8
通讯作者：
Göthert, M
中科院分区：
文献类型：
--
作者：
Molderings, GJ;Likungu, J;Göthert, M
背景-由于对人类外周交感神经系统中动作电位诱导的去甲肾上腺素释放所涉及的钙通道类型的了解很少，我们研究了哪种类型的钙通道在人类心脏组织的交感神经中具有重要的功能。确定控制由透壁电刺激诱发的[H-3]去甲肾上腺素释放的钙通道的类型。[H-3]去甲肾上腺素的释放几乎被0.2 μ mol/L ω-芋螺毒素GVIA（一种N型通道的选择性阻断剂）所消除，但不被0.1 μ mol/L ω-龙舌兰毒素IVA（一种P型和Q型通道的选择性阻断剂）所改变。米贝拉地尔浓度为0.3 - 3 μ mol/L的T-Ca（Ⅱ）（一种T-型和N-型钙通道阻滞剂）以频率和钙依赖的方式减少诱发的氚溢出，而浓度为0.1 - 10 μ mol/L的T-Ca（Ⅱ）、地尔硫卓和维拉帕米则以频率和钙依赖的方式减少诱发的氚溢出。（L型通道的选择性阻断剂）无效，结论：心脏交感神经释放去甲肾上腺素是由N型钙离子内流触发的，而不是L型和P/Q型钙离子通道。在临床相关浓度下，米贝拉地尔对去甲肾上腺素释放的抑制作用可能是由于其对N型Ca 2+通道的阻断作用。米贝拉地尔的这种性质在已经或仍然在治疗上应用的钙通道阻滞剂中是独特的，并且可能相当大地有助于其在体内的轻微负性变时作用。
Background-Because knowledge about the type of calcium channels involved in action potential-induced norepinephrine release from the human peripheral sympathetic nervous system is sparse, we investigated which types of calcium channels are functionally important in the sympathetic nerves of human cardiac tissue.Methods and Results-In superfused segments of human right atrial appendages, the type of calcium channels that control [H-3]norepinephrine release evoked by transmural electrical stimulation was determined. [H-3]norepinephrine release was almost abolished by 0.2 mu mol/L omega-conotoxin GVIA (a selective blocker of N-type channels) but was not modified by 0.1 mu mol/L omega-agatoxin IVA (a selective blocker of P- and Q-type channels). Mibefradil (a T-type and N-type calcium channel blocker) at concentrations of 0.3 to 3 mu mol/L reduced the evoked tritium overflow in a frequency- and calcium-dependent manner, whereas 0.1 to 10 mu mol/L amlodipine, diltiazem, and verapamil (selective blockers of L-type channels) were ineffective,Conclusions-Norepinephrine release from cardiac sympathetic nerves is triggered by Ca2+ influx via N-type but not L- and P/Q-type calcium channels. The inhibitory effect of mibefradil on norepinephrine release at clinically relevant concentrations is probably due to its blocking action on N-type Ca2+ channels. This property of mibefradil is unique among the calcium channel blockers that have been or still are therapeutically applied and may considerably contribute to its slight negative chronotropic effect in vivo.