Kolaj M, Renaud L P
Neurology and Neurosciences, Loeb Health Research Institute, Ottawa Hospital--Civic Site and University of Ottawa, 1053 Carling Avenue, Ottawa, Ontario, Canada K1Y 4E9.
Neuropharmacology. 2001 Sep;41(4):472-9. doi: 10.1016/s0028-3908(01)00090-9.
The median preoptic (MnPO) nucleus, a key CNS site for hydromineral and cardiovascular homeostasis, receives a dense norepinephrine innervation from brainstem autonomic centers. Since norepinephrine is known to influence neuronal excitability by modulating calcium channel function, we applied whole cell patch clamp techniques to study calcium currents in 116 dissociated MnPO neurons, including 30 cells identified by a retrograde label as projecting to the hypothalamic paraventricular nucleus. Norepinephrine (3-50 microM) suppressed high-voltage-activated calcium currents (HVA I(Ca)) in 80% of cells, selectively blockable by yohimbine and mimicked by UK14,304 and clonidine. The norepinephrine effect was relieved by strong prior depolarization, indicating a voltage-dependent component. Intracellular GTP-gamma-S blocked the effect. Blockade by extracellular NEM suggested involvement of pertussis-toxin sensitive G-proteins. Based on pharmacological properties, these HVA I(Ca)s had the following composition: 40-45% N-type (blockable by omega-conotoxin GVIA); 20-25% L-type (blockable by nimodipine); 15-20% P/Q-type (blockable by omega-agatoxin IVA). Since approximately 75% of the norepinephrine effect was blockable with omega-conotoxin GVIA, we conclude that postsynaptic alpha(2) adrenoceptors preferentially suppress N-type calcium channels, revealing a novel mechanism whereby norepinephrine can modulate excitability in MnPO neurons.
视前正中核（MnPO）是水盐和心血管稳态的关键中枢神经系统部位，接受来自脑干自主神经中枢的密集去甲肾上腺素能神经支配。由于已知去甲肾上腺素通过调节钙通道功能来影响神经元兴奋性，我们应用全细胞膜片钳技术研究了116个解离的MnPO神经元中的钙电流，其中30个细胞通过逆行标记被鉴定为投射到下丘脑室旁核。去甲肾上腺素（3 - 50 microM）抑制了80%细胞中的高电压激活钙电流（HVA I(Ca)），育亨宾可选择性阻断该作用，UK14,304和可乐定可模拟该作用。去甲肾上腺素的作用在强烈的预去极化后得到缓解，表明存在电压依赖性成分。细胞内GTP-γ-S可阻断该作用。细胞外NEM的阻断表明百日咳毒素敏感的G蛋白参与其中。基于药理学特性，这些HVA I(Ca)具有以下组成：40 - 45%为N型（可被ω-芋螺毒素GVIA阻断）；20 - 25%为L型（可被尼莫地平阻断）；15 - 20%为P/Q型（可被ω-阿加毒素IVA阻断）。由于约75%的去甲肾上腺素作用可被ω-芋螺毒素GVIA阻断，我们得出结论，突触后α(2)肾上腺素能受体优先抑制N型钙通道，揭示了去甲肾上腺素调节MnPO神经元兴奋性的一种新机制。
