Involvement of voltage-dependent Ca2+ channel β3 subunit in the autonomic control of heart rate variability
Involvement of voltage-dependent Ca2+ channel β3 subunit in the autonomic control of heart rate variability
复制标题
DOI：
10.1159/000091495
复制
发表时间：
2006-01-01
期刊：
影响因子：
3.1
通讯作者：
Iijima, T
中科院分区：
文献类型：
--
作者：
Wu, TW;Ono, K;Iijima, T
从交感神经末梢释放去甲肾上腺素依赖于通过神经元电压门控N型Ca 2+通道的Ca 2+内流。Ca 2+通道的辅助β 3亚基（Ca-V β 3）优先与α 1B亚基结合形成N型Ca 2+通道，因此预期在刺激诱发的去甲肾上腺素释放中发挥功能性作用。在这项研究中，我们采用了Ca-V β（3）-null，Cav β（3）-overexpressing（Ca-V β（3）-Tg）和野生型（WT）小鼠来研究Ca-V β（3）在体内心率交感神经调节中的可能作用。遥测用于监测ECG，并进行时域和频域分析以评估心率变异性。在频域分析中，利用快速傅立叶变换算法计算RR间期序列的功率谱密度。与Ca-V beta（3）-null和WT小鼠相比，Ca-V beta（3）-Tg小鼠的静息心率增加。过表达Ca-V β 3的小鼠表现出心率变异性降低，这是通过RR间期标准差的时域分析来测量的。在频域分析中，与WT和Ca-V beta（3）-null小鼠相比，Ca-V beta（3）-Tg小鼠显示出降低的谱功率。用美托洛尔阻断β-肾上腺素能受体可降低所有基因型小鼠的心率，但降低的程度在Ca-V β（3）-Tg小鼠中最为明显。另一方面，在WT和Ca-v β（3）-Tg小鼠中，对交感神经阻滞（阿托品）的反应使光谱功率降低。这些结果表明Ca-V β（3）在调节交感神经信号传导中的功能作用。版权所有（C）2006 S Karger AG，巴塞尔。
Noradrenaline release from sympathetic nerve terminals is dependent on Ca2+ entry through neuronal voltage-gated N-type Ca2+ channels. The accessory beta(3) subunits of Ca2+ channels (Ca-V beta(3)) are preferentially associated with the alpha(1B) subunit to form N-type Ca2+ channels, and are therefore expected to play a functional role in the stimulation-evoked release of noradrenaline. In this study, we employed Ca-v beta(3)-null, Cav beta(3)-overexpressing (Ca-V beta(3)-Tg), and wild-type (WT) mice to investigate the possible roles of Ca-V beta(3) in the sympathetic regulation of heart rate in vivo. Telemetry was used to monitor the ECG and both time and frequency domain analyses were carried out to evaluate heart rate variability. In the frequency domain analysis, power spectral density of the RR interval series was computed using the fast Fourier transform algorithm. The resting heart rate was increased in Ca-V beta(3)-Tg mice compared with both Ca-V beta(3)-null and WT mice. Mice overexpressing Ca-V beta(3) displayed decreased heart rate variability, which was measured by the time domain analysis of the standard deviation of RR intervals. In the frequency domain analysis, Ca-V beta(3)-Tg mice showed decreased spectral powers compared with WT and Ca-V beta(3)-null mice. Pharmacological blockade of beta-adrenergic receptors with metoprolol decreased the heart rate in all genotypes, but the extent of the decrease was most obvious in Ca-V beta(3)-Tg mice. On the other hand, the spectral powers were decreased in response to para-sympathetic blockade (atropine) in WT and Ca-v beta(3)-Tg mice. These results indicate the functional roles of Ca-V beta(3) in regulating sympathetic nerve signaling. Copyright (C) 2006 S Karger AG, Basel.