在成年大鼠迷走神经传入神经元中，血管紧张素II对钙电流的抑制作用独立于血管紧张素II 1型受体（ATR1）的激活。

Angiotensin II inhibition of Ca2+ currents is independent of ATR1 angiotensin II receptor activation in rat adult vagal afferent neurons.

作者信息

Moreira Thaís Helena, Rodrigues Andréia Laura, Beirão Paulo Sérgio L, dos Santos Robson Augusto, Santos Cruz Jader

机构信息

Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, ICB-UFMG-Bloco K4-sala 167 Belo Horizonte, MG CEP 31270-901, Brazil.

出版信息

Auton Neurosci. 2005 Feb 7;117(2):79-86. doi: 10.1016/j.autneu.2004.11.002.

DOI:10.1016/j.autneu.2004.11.002

PMID:15664560

Abstract

Angiotensin II (ANG II) has the ability to modulate the activity of neurons involved in the cardiovascular regulation. One effective way of doing that is by changing calcium currents. In the present study, we investigated the effects of ANG II on high-voltage-activated (HVA) Ca2+ currents measured in adult vagal afferent neurons using the whole-cell patch-clamp technique. In addition, we demonstrated the presence of ATR1 and ATR2 receptors mRNA at nodose neurons using conventional reverse transcriptase-polymerase chain reaction (RT-PCR). ANG II (100 nM) decreased the HVA Ca2+ current (peak current recorded at 0 mV: -60.9+/-8.7 pA/pF in control conditions versus -31.9+/-5.7 pA/pF in the presence of ANG II) and shifted the Ca2+ current activation to a more negative membrane potential (control V0.5=-12.5+/-1.5 mV versus -18.4+/-2.8 mV during perfusion with ANG II). Losartan (500 nM) was not able to prevent the ANG II effect on the HVA Ca2+ current making unlikely the involvement of the ATR1 receptor. When ANG II was perfused in the continuous presence of saralasin, a non-selective ANG II receptor antagonist, we observed a faster but transient inhibition of HVA Ca2+ current. The inhibition was not sustained as observed when we applied ANG II alone and the HVA Ca2+ current recovered with time reaching levels close to the control. Unexpectedly, treatment with the ATR2 blocker PD 123,319 (500 nM) caused a significant inhibition on the HVA Ca2+ current making rather difficult any further conclusions. The above results allow us to conclude that ANG II induced inhibition on the HVA Ca2+ current is probably not via ATR1 receptor activation.

摘要

血管紧张素 II（ANG II）能够调节参与心血管调节的神经元的活动。实现这一目的的一种有效方式是改变钙电流。在本研究中，我们使用全细胞膜片钳技术研究了 ANG II 对成年迷走神经传入神经元中测量的高电压激活（HVA）Ca2+电流的影响。此外，我们使用传统逆转录聚合酶链反应（RT-PCR）证明了在结状神经元中存在 ATR1 和 ATR2 受体 mRNA。ANG II（100 nM）降低了 HVA Ca2+电流（在 0 mV 记录的峰值电流：对照条件下为-60.9±8.7 pA/pF，而在存在 ANG II 时为-31.9±5.7 pA/pF），并将 Ca2+电流激活转移到更负的膜电位（对照 V0.5=-12.5±1.5 mV，而在灌注 ANG II 期间为-18.4±2.8 mV）。氯沙坦（500 nM）无法阻止 ANG II 对 HVA Ca2+电流的影响，这使得 ATR1 受体不太可能参与其中。当在非选择性 ANG II 受体拮抗剂沙拉新持续存在的情况下灌注 ANG II 时，我们观察到 HVA Ca2+电流的抑制更快但短暂。这种抑制不像我们单独应用 ANG II 时那样持续，并且 HVA Ca2+电流随时间恢复，达到接近对照的水平。出乎意料的是，用 ATR2 阻滞剂 PD 123,319（500 nM）处理对 HVA Ca2+电流产生了显著抑制，这使得进一步得出结论变得相当困难。上述结果使我们得出结论，ANG II 诱导的对 HVA Ca2+电流的抑制可能不是通过 ATR1 受体激活。